Page 1 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
Accession # 1 Reference
NGV4(from NGC) Lin et al. 1994
DQ518643
P-GV3(from PUO-218) Lin et al. 1994
DQ518667
AY648301 rDEN4 Blaney et al. 2003
AY648301 rDEN4 Blaney et al. 2003
AY648301 rDEN4 Blaney et al. 2003
AY648301 rDEN4 Blaney et al. 2003
AY648301 rDEN4 Blaney et al. 2003
AY648301 rDEN4 Blaney et al. 2003
AY648301 rDEN4 Blaney et al. 2003
AY648301 rDEN4 Blaney et al. 2003
AY648301 rDEN4 Blaney et al. 2003
AY648301 rDEN4 Blaney et al. 2003
TBE V-IC3 Holzmann et al. 1997
U39292
U39292 TBE V-IE3 Holzmann et al. 1997
U39292 TBE V-IO3 Holzmann et al. 1997
not identified WNI-568 Chambers et al. 1998
not identified WNI-567 Chambers et al. 1998
not identified WNI-25 Chambers et al. 1998
not identified WNI-25A Chambers et al. 1998
not identified DEN3 via Mab 1H9 Serafin & Aaskov 2001
PRS 225489 DEN2 (NGC) Via Mab 4G2 Serafin & Aaskov 2001
M29095 DEN2 Mexican Small plaque 3 Sanchez & Ruiz 1996
L04561 DEN2 Mexican Medium plaque 1 Sanchez & Ruiz 1996
L04561 DEN2 Mexican Large plaque 2 Sanchez & Ruiz 1996
L04561 DEN2 Mexican Small plaque 2 Sanchez & Ruiz 1996
L04561 DEN2 Mexican Small plaque 1 Sanchez & Ruiz 1996
L04561 DEN2 Mexican Small plaque 4 Sanchez & Ruiz 1996
L04561 DEN2 Mexican Large plaque 3 Sanchez & Ruiz 1996
L04561 DEN2 Mexican Large plaque 4 Sanchez & Ruiz 1996
not identified DEN Roehrig 2003-Lin et al. 1994
not identified DEN Roehrig 2003-Beasley&Askov, 2001
not identified DEN Roehrig 2003-Lok et al., 2001
not identified DEN Roehrig 2003
not identified DEN Roehrig 2003
not identified DEN Roehrig 2003
not identified DEN Roehrig 2003
not identified DEN Roehrig 2003
Page 2 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
not identified JE Roehrig 2003-Hasegawa et al., 1992
not identified JE Roehrig 2003-Cecilia & Gould, 1991
not identified JE Roehrig 2003-Morita et al., 2001
not identified JE Roehrig 2003
not identified JE Roehrig 2003
not identified JE Roehrig 2003
not identified LI Roehrig 2003-Gao et al., 1994
not identified LI Roehrig 2003-Jiang et al. 1993
not identified LI Roehrig 2003
not identified MVE Roehrig 2003-McMinn et al. 1995
not identified MVE Roehrig 2003
not identified MVE Roehrig 2003
not identified MVE Roehrig 2003
not identified MVE Roehrig 2003
not identified TBE Roehrig 2003-Holzmann et al. 1997, Mandl et al,
1989
not identified TBE Roehrig 2003
not identified TBE Roehrig 2003
not identified TBE Roehrig 2003
not identified TBE Roehrig 2003
not identified TBE Roehrig 2003
not identified TBE Roehrig 2003
not identified TBE Roehrig 2003
not identified TBE Roehrig 2003
not identified YF Roehrig 2003-Lobigs et al., 1987
not identified YF Roehrig 2003-Ryman et al, 1997
not identified YF Roehrig 2003
not identified YF Roehrig 2003
not identified YF Roehrig 2003
not identified DEN3 1047MP10 Lee et al. 1997
direct isolates DEN3 1153MP10 Lee et al. 1997
from patients
direct isolates DEN3 1239MP10 Lee et al. 1997
from patients
direct isolates DEN3 1047V1P10 Lee et al. 1997
from patients
direct isolates DEN3 1047V2P10 Lee et al. 1997
from patients
direct isolates DEN3 1153V1P10 Lee et al. 1997
from patients
direct isolates DEN3 1153V2P10 Lee et al. 1997
from patients
Page 3 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
Den3 1239V1P10 Lee et al. 1997
direct isolates DEN3 1239V2P10 Lee et al. 1997
from patients
direct isolates DEN3 1153CP5 Lee et al. 1997
from patients
direct isolates DEN3 1239CP5 Lee et al. 1997
from patients
direct isolates KUN NS2A1/MRM 61C Liu et al. 2004
from patients
D00246 KUN NS2A2/MRM 61C Liu et al. 2004
D00246 KUN NS5/MRM 61C Liu et al. 2004
D00246 rDEN4-2A-5 Hanley et al. 2003
AF326825 rDen4delta30-7129 Hanley et al. 2003
AF326827 rDEN4-7129 Hanley et al. 2003
AF326825 rDEN4 (could also be AF326825) Hanley et al. 2001
AF326573 rDEN4 (could also be AF326825) Hanley et al. 2001
AF326573 rDEN4 (could also be AF326825) Hanley et al. 2001
AF326573 rDEN4 (could also be AF326825) Hanley et al. 2001
AF326573 rDEN4 (could also be AF326825) Hanley et al. 2001
AF326573 rDEN4 (could also be AF326825) Hanley et al. 2001
AF326573 rDEN4 (could also be AF326825) Hanley et al. 2001
AF326573 rDEN4 (could also be AF326825) Hanley et al. 2001
AF326573 rDEN4 (could also be AF326825) Hanley et al. 2001
AF326573 rDEN4 (could also be AF326825) Hanley et al. 2001
AF326573 rDEN4 (could also be AF326825) Hanley et al. 2001
AF326573 rDEN4 (could also be AF326825) Hanley et al. 2001
AF326573 rDEN4 (could also be AF326825) Hanley et al. 2001
AF326573 rDEN4 (could also be AF326825) Hanley et al. 2001
AF326573 rDEN4 (could also be AF326825) Hanley et al. 2001
AF326573 rDEN4 (could also be AF326825) Hanley et al. 2001
AF326573 rDEN4 (could also be AF326825) Hanley et al. 2001
AF326573 rDEN4 (could also be AF326825) Hanley et al. 2001
AF326573 rDEN4 (could also be AF326825) Hanley et al. 2001
AF326573 rDEN4 (could also be AF326825) Hanley et al. 2001
Page 4 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
AF326573 rDEN4 (could also be AF326825) Hanley et al. 2001
AF326573 rDEN4 (could also be AF326825) Hanley et al. 2001
AF326573 rDEN4 (could also be AF326825) Hanley et al. 2001
AF326573 rDEN4 (could also be AF326825) Hanley et al. 2001
AF326573 rDEN4 (could also be AF326825) Hanley et al. 2001
AF326573 rDEN4 (could also be AF326825) Hanley et al. 2001
AF326573 rDEN4 (could also be AF326825) Hanley et al. 2001
AF326573 rDEN4 (could also be AF326825) Hanley et al. 2001
AF326573 rDEN4 (could also be AF326825) Hanley et al. 2001
AF326573 rDEN4 (could also be AF326825) Hanley et al. 2001
AF326573 rDEN4 (could also be AF326825) Hanley et al. 2001
AF326573 rDEN4 (could also be AF326825) Hanley et al. 2001
AF326573 rDEN4 (could also be AF326825) Hanley et al. 2001
AF326573 rDEN4 (could also be AF326825) Hanley et al. 2001
AF326573 rDEN4delta30-4995 Hanley et al. 2004
AF326827 rDEN4delta30-8092 Hanley et al. 2004
AF326827 rDEN4delta30-10634 Hanley et al. 2004
AF326827 rDEN4delta30-200-201 Hanley et al. 2004
AF326827 rDEN4delta30-436-437 Hanley et al. 2004
AF326827 rDEN4-4891 Blaney Jr. et al. 2003
AY648301 rDEN4-4995 Blaney Jr. et al. 2003
AY648301 rDEN4-7153 Blaney Jr. et al. 2003
AY648301 rDEN4-7162 Blaney Jr. et al. 2003
AY648301 rDEN4-7163 Blaney Jr. et al. 2003
AY648301 rDEN4-7182 Blaney Jr. et al. 2003
AY648301 rDEN4-7546 Blaney Jr. et al. 2003
AY648301 rDEN4-7630 Blaney Jr. et al. 2003
AY648301 rDEN4-10279 Blaney Jr. et al. 2003
AY648301 rDEN4-10275 Blaney Jr. et al. 2003
Page 5 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
AY648301 rDEN2/4delta30-4891 Blaney Jr. et al. 2003
rDEN2/4delta30-4995 Blaney Jr. et al. 2003
AY744147
rDEN2/4delta30-7153 Blaney Jr. et al. 2003
AY744147
rDEN2/4delta30-7162 Blaney Jr. et al. 2003
AY744147
rDEN2/4delta30-7163 Blaney Jr. et al. 2003
AY744147
rDEN2/4delta30-7182 Blaney Jr. et al. 2003
AY744147
rDEN2/4delta30-7546 Blaney Jr. et al. 2003
AY744147
rDEN2/4delta30-7630 Blaney Jr. et al. 2003
AY744147
rDEN2/4delta30-10279 Blaney Jr. et al. 2003
AY744147
rDEN2/4delta30-10275 Blaney Jr. et al. 2003
AY744147
JEVdelta39-44 Yoshio et al., 2004
JEVG42 Yoshio et al., 2004
JEV M4243 Yoshio et al., 2004
rDEN1mutF, derived from Western Pacific,74 Whitehead et al., 2003
rDEN1delta30, derived from Western Pacific,74 Whitehead et al., 2003
814669 DEN4 3'd 172-143 Men et al., 1996
814669 DEN4 3'd 172-113 Men et al., 1996
814669 DEN4 3'd 172-83 Men et al., 1996
814669 DEN4 3'd 243-183 Men et al., 1996
814669 DEN4 3'd 303-183 Men et al., 1996
Page 6 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
814669 DEN4 3'd 333-183 Men et al., 1996
814669 DEN4 3'd 384-183 Men et al., 1996
814669 DEN4 3'd 384-183/172-113 Men et al., 1996
814669 WNV, Kunjin strain Liu et al., 2006
NC_001563 Western TBE strain Neudoerfl c(delta28-43) – before Koffler et al, 2002
passaging
U27495 Western TBE strain Neudoerfl c(delta28-46) – after Koffler et al, 2002
passaging
U27495 Western TBE strain Neudoerfl c(delta28-48) – after Koffler et al, 2002
passaging
U27495 Western TBE strain Neudoerfl c(delta28-48/Q70L) Koffler et al, 2002
U27495 Western TBE strain Neudoerfl c(delta28-48/Du78-85) Koffler et al, 2002
U27495 Western TBE strain Neudoerfl c(delta28-48) – after Koffler et al, 2002
passaging
U27495 Western TBE strain Neudoerfl c(delta28-48) – after Koffler et al, 2002
passaging
U27495 Western TBE strain Neudoerfl c(delta28-48) – after Koffler et al, 2002
passaging
U27495 Western TBE strain Neudoerfl c(delta28-48) – after Koffler et al, 2002
passaging
U27495 Western TBE strain Neudoerfl c(delta28-48) – after Koffler et al, 2002
passaging
U27495 Western TBE strain Neudoerfl c(delta28-54) – after Koffler et al, 2002
passaging
U27495 Western TBE strain Neudoerfl c(delta28-54) – after Koffler et al, 2002
passaging
U27495 Western TBE strain Neudoerfl c(delta28-54) – after Koffler et al, 2002
passaging
U27495 Western TBE strain Neudoerfl c(delta28-57) – after Koffler et al, 2002
passaging
U27495 Western TBE strain Neudoerfl c(delta28-57) – after Koffler et al, 2002
passaging
U27495 Western TBE strain Neudoerfl c(delta28-54) – before Koffler et al, 2002
passaging
U27495 Western TBE strain Neudoerfl c(delta28-57) – before Koffler et al, 2002
passaging
Page 7 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
U27495 Western TBE strain Neudoerfl c(delta28-46) – before Koffler et al, 2002
passaging
U27495 Western TBE strain Neudoerfl c(delta28-48) – before Koffler et al, 2002
passaging
U27495 DEN2 6b2 escape mutant Lok et al., 2001
M29095/ New DEN2 6b2 passage control Lok et al., 2001
Guinea C
(Igarashi, 1978)
M29095/ New DEN2 10F2 escape mutant Lok et al., 2001
Guinea C
(Igarashi, 1978)
M29095/ New DEN2 10F2 passage control Lok et al., 2001
Guinea C
(Igarashi, 1978)
M29095/ New YF NS2Aalpha QST Kummerer and Rice, 2002
Guinea C
(Igarashi, 1978)
NC_002031 YF NS2Alpha QKV Kummerer and Rice, 2002
NC_002031 YF NS2Alpha QQT Kummerer and Rice, 2002
NC_002031 YF NS2Aalpha QET Kummerer and Rice, 2002
NC_002031 YF NS2Aalpha QRT Kummerer and Rice, 2002
NC_002031 YF NS2Aalpha QIT Kummerer and Rice, 2002
NC_002031 YF NS2Aalpha SKT Kummerer and Rice, 2002
NC_002031 YF NS2Aalpha RRS Kummerer and Rice, 2002
NC_002031 YF NS2Aalpha KLEEG reconstructed mutant Kummerer and Rice, 2002
NC_002031 YF NS2Aalpha KRET reconstructed mutant Kummerer and Rice, 2002
NC_002031 YF NS2Aalpha RRSTG reconstructed mutant Kummerer and Rice, 2002
NC_002031 YF NS2Aalpha SKT D343V double mutant Kummerer and Rice, 2002
NC_002031 YF NS2Aalpha SKT D343A double mutant Kummerer and Rice, 2002
NC_002031 YF NS2Aalpha SKT D343G double mutant Kummerer and Rice, 2002
NC_002031 YF NS3 D343V Kummerer and Rice, 2002
NC_002031 YF NS3 D343A Kummerer and Rice, 2002
NC_002031 YF NS3 D343G Kummerer and Rice, 2002
NC_002031 YF NS1 SB (YFiv5.2) Muylaert et al., 1996
YF NS1 G1a (YFiv5.2) Muylaert et al., 1996
NC_002031
YF NS1 G1b (YFiv5.2) Muylaert et al., 1996
NC_002031
YF NS1 G2a (YFiv5.2) Muylaert et al., 1996
NC_002031
Page 8 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
YF NS1 G2b (YFiv5.2) Muylaert et al., 1996
NC_002031
YF NS1 G1aG2a (YFiv5.2) Muylaert et al., 1996
NC_002031
YF NS1 G1bG2b (YFiv5.2) Muylaert et al., 1996
NC_002031
M29095 New pSV.NS2B/3 17-20 Matusan et al., 2001
Guinea C, Arias et
al. (1993), Teo &
Wright (1997),
Rice (1996),
Yusoff et al.
(2000)
M29095 New pSV.NS2B/3 32-36 Matusan et al., 2001
Guinea C, Arias et
al. (1993), Teo &
Wright (1997),
Rice (1996),
Yusoff et al.
(2000)
M29095 New pSVNS2B/3 63-66 Matusan et al., 2001
Guinea C, Arias et
al. (1993), Teo &
Wright (1997),
Rice (1996),
Yusoff et al.
(2000)
M29095 New pSVNS2B/3 95-96 Matusan et al., 2001
Guinea C, Arias et
al. (1993), Teo &
Wright (1997),
Rice (1996),
Yusoff et al.
(2000)
M29095 New pSVNS2B/3 179-181 Matusan et al., 2001
Guinea C, Arias et
al. (1993), Teo &
Wright (1997),
Rice (1996),
Yusoff et al.
(2000)
M29095 Dengue 2 NGC Kroshewski et al 2008
M29095 Dengue 2 NGC Kroshewski et al 2008
M29095 Dengue 2 NGC Kroshewski et al 2008
Page 9 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
M29095 Dengue 2 NGC Kroshewski et al 2008
M29095 Dengue 2 NGC Kroshewski et al 2008
M29095 Dengue 2 NGC Kroshewski et al 2008
M29095 Dengue 2 NGC Kroshewski et al 2008
M29095 Dengue 2 NGC Kroshewski et al 2008
M29095 Dengue 2 NGC Kroshewski et al 2008
M29095 Dengue 2 NGC Kroshewski et al 2008
M29095 Dengue 2 NGC Kroshewski et al 2008
M29095 Dengue 2 NGC Kroshewski et al 2008
M29095 Dengue 2 NGC Kroshewski et al 2008
M29095 Dengue 2 NGC Kroshewski et al 2008
M29095 Dengue 2 NGC Kroshewski et al 2008
M29095 WN pFLWNV 5'-3627 Zhang et al 2008
AF404756 WN pFLWNV 5'-3627 Zhang et al 2008
AF404756 WN pFLWNV 5'-3627 Zhang et al 2008
AF404756 WN pFLWNV 5'-3627 Zhang et al 2008
AF404756 WN pFLWNV 5'-3627 Zhang et al 2008
AF404756 WN pFLWNV 5'-3627 Zhang et al 2008
AF404756 WN pFLWNV 5'-3627 Zhang et al 2008
AF404756 WN pFLWNV 5'-3627 Zhang et al 2008
AF404756 WN pFLWNV 5'-3627 Zhang et al 2008
AF404756 WN pFLWNV 5'-3627 Zhang et al 2008
AF404756 WN pFLWNV 5'-3627 Zhang et al 2008
AF404756 D2-VEN90 Leitmeyer et al., 1999
AF100466 D2-VEN91 Leitmeyer et al., 1999
AF100150 D2-MEX95 Leitmeyer et al., 1999
AF100147 D2-MEX97 Leitmeyer et al., 1999
AF100146 D2-THAI96A Leitmeyer et al., 1999
AF100463 D2-THAI96B Leitmeyer et al., 1999
AF100464 D2-THAI95A Leitmeyer et al., 1999
AF100461 D2-THAI94A Leitmeyer et al., 1999
AF100459 D2-THAI94B Leitmeyer et al., 1999
AF100460 D2-THAI95B Leitmeyer et al., 1999
AF100462 D2-PR81 Leitmeyer et al., 1999
Page 10 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
AF100149 D2-COL86 Leitmeyer et al., 1999
AF100458 D2-MEX83 Leitmeyer et al., 1999
AF100151 D2-VEN90B Leitmeyer et al., 1999
AF100466 D2-VEN87 Leitmeyer et al., 1999
AF100465 D2-MEX92 Leitmeyer et al., 1999
AF100469 D2-MEX92B Leitmeyer et al., 1999
AF100148 D2-PERU95 Leitmeyer et al., 1999
AF100467 YF-17D Nickells and Chambers, 2003
X03700 KUN Leung et al 2008
AY274504 or KUN Leung et al 2008
D00246
AY274504 or KUN Leung et al 2008
D00246
AY274504 or KUN Leung et al 2008
D00246
AY274504 or KUN Leung et al 2008
D00246
AY274504 or KUN Leung et al 2008
D00246
AY274504 or KUN Leung et al 2008
D00246
AY274504 or KUN Leung et al 2008
D00246
U87411 DEN2 strain 16681 Alvarez et al 2008
U87411 DEN2 strain 16681 Alvarez et al 2008
U87411 DEN2 strain 16681 Alvarez et al 2008
U87411 DEN2 strain 16681 Alvarez et al 2008
U87411 DEN2 strain 16681 Alvarez et al 2008
U87411 DEN2 strain 16681 Alvarez et al 2008
U87411 DEN2 strain 16681 Alvarez et al 2008
U87411 DEN2 strain 16681 Alvarez et al 2008
U87411 DEN2 strain 16681 Alvarez et al 2008
U87411 DEN2 strain 16681 Alvarez et al 2008
U87411 DEN2 strain 16681 Alvarez et al 2008
U87411 DEN2 strain 16681 Alvarez et al 2008
U87411 DEN2 strain 16681 Alvarez et al 2008
U87411 DEN2 strain 16681 Alvarez et al 2008
U87411 DEN2 strain 16681 Alvarez et al 2008
U87411 DEN2 strain 16681 Alvarez et al 2008
U87411 DEN2 strain 16681 Alvarez et al 2008
U87411 DEN2 strain 16681 Alvarez et al 2008
U87411 DEN2 strain 16681 Alvarez et al 2008
U87411 DEN2 strain 16681 Alvarez et al 2008
U87411 DEN2 strain 16681 Alvarez et al 2008
Page 11 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
U87411 DEN2 strain 16681 Alvarez et al 2008
U87411 DEN2 strain 16681 Alvarez et al 2008
U87411 DEN2 strain 16681 Alvarez et al 2008
U87411 DEN2 strain 16681 Alvarez et al 2008
U87411 DEN2 strain 16681 Alvarez et al 2008
AB178040 rDEN 1-NIID02-20 Tajima et al 2008
AB178040 rDEN 1-NIID02-20 Tajima et al 2008
AB178040 rDEN 1-NIID02-20 Tajima et al 2008
AB178040 WN25A, WN25A.9 Chambers et al. 2008
AF404756 Rluc-Rep cDNA clone/pGEM-5NTR Zhang et al 2008
AF404756 Rluc-Rep cDNA clone/pGEM-5NTR Zhang et al 2008
AF404756 Rluc-Rep cDNA clone/pGEM-5NTR Zhang et al 2008
AF404756 Rluc-Rep cDNA clone/pGEM-5NTR Zhang et al 2008
AF404756 Rluc-Rep cDNA clone/pGEM-5NTR Zhang et al 2008
AF404756 Rluc-Rep cDNA clone/pGEM-5NTR Zhang et al 2008
AF404756 pFLWNV Zhang et al 2008
AF404756 pFLWNV Zhang et al 2008
AF404756 pFLWNV Zhang et al 2008
AF404756 pFLWNV Zhang et al 2008
AF404756 pFLWNV Zhang et al 2008
AF404756 pFLWNV Zhang et al 2008
AF196835 WNV Botha et al 2008
AF346318 WNV Botha et al 2008
EF429197 WNV Botha et al 2008
AB196923 JEVAT31strain-pMWJEATG1 Yamashiita et al 2008
AB196923 JEVAT31strain-pMWJEATG1 Yamashiita et al 2008
AB196923 JEVAT31strain-pMWJEATG1 Yamashiita et al 2008
AB196923 JEVAT31strain-pMWJEATG1 Yamashiita et al 2008
AB196923 JEVAT31strain-pMWJEATG1 Yamashiita et al 2008
Page 12 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
not identified pYF23 from cDNA clone of pACNR/FLYF Patkar and Kuhn 2008
not identified pYF23 from cDNA clone of pACNR/FLYF Patkar and Kuhn 2008
not identified pYF23 from cDNA clone of pACNR/FLYF Patkar and Kuhn 2008
not identified pYF23 from cDNA clone of pACNR/FLYF Patkar and Kuhn 2008
not identified pYF23 from cDNA clone of pACNR/FLYF Patkar and Kuhn 2008
not identified pYF23 from cDNA clone of pACNR/FLYF Patkar and Kuhn 2008
not identified pYF23 from cDNA clone of pACNR/FLYF Patkar and Kuhn 2008
AY648961 rDEN3-p3-7164 (includes adaption mut. V115A) Blaney Jr. et al. 2007
AY648961 rDEN3-p3-7164 (includes adaption mut. V115A) Blaney Jr. et al. 2007
AY648961 rDEN3-p3-7164 (includes adaption mut. V115A) Blaney Jr. et al. 2007
AY648961 rDEN3-p3-7164 (includes adaption mut. V115A) Blaney Jr. et al. 2007
AY648961 rDEN3-p3-7164 (includes adaption mut. V115A) Blaney Jr. et al. 2007
AY648961 rDEN3-p3-7164 (includes adaption mut. V115A) Blaney Jr. et al. 2007
AY648961 rDEN3-p3-7164 (includes adaption mut. V115A) Blaney Jr. et al. 2007
AY648961 rDEN3-p3-7164 (includes adaption mut. V115A) Blaney Jr. et al. 2007
AY648961 rDEN3-p3-7164 (includes adaption mut. V115A) Blaney Jr. et al. 2007
AY648961 rDEN3-p3-7164 (includes adaption mut. V115A) Blaney Jr. et al. 2007
AY648961 rDEN3-p3-7164 (includes adaption mut. V115A) Blaney Jr. et al. 2007
not identified WNR-CNS1-5luc replicon Suzuki et al 2008
Page 13 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
not identified WNR-CNS1-5luc replicon Suzuki et al 2008
not identified WNR-CNS1-5luc replicon Suzuki et al 2008
not identified WNR-CNS1-5luc replicon Suzuki et al 2008
not identified WNR-CNS1-5luc replicon Suzuki et al 2008
not identified WNR-CNS1-5luc replicon Suzuki et al 2008
not identified WNR-CNS1-5luc replicon Suzuki et al 2008
not identified WNR-CNS1-5luc replicon Suzuki et al 2008
not identified WNR-CNS1-5luc replicon Suzuki et al 2008
not identified WNR-CNS1-5luc replicon Suzuki et al 2008
not identified WNR-CNS1-5luc replicon Suzuki et al 2008
not identified WNR-CNS1-5luc replicon Suzuki et al 2008
not identified WNR-CNS1-5luc replicon Suzuki et al 2008
not identified WNR-CNS1-5luc replicon Suzuki et al 2008
not identified WNR-CNS1-5 no luc replicon Suzuki et al 2008
not identified WNV genome Suzuki et al 2008
not identified WNR-CNS1-5luc replicon Suzuki et al 2008
not identified WNR-CNS1-5luc no luc replicon Suzuki et al 2008
AY303793-4 JE-CJN Chiou and Chen 2007
AY303793-4 JE-CJN Chiou and Chen 2007
AY303793-4 JE-CH1392 Chiou and Chen 2006
AF254451 JE-CH1392 Chiou and Chen 2007
AF254452 JE-T1P1 Chiou and Chen 2007
AY303791-2 or JE-T1P1 Chiou and Chen 2007
AF254453
AY303791-2 or JE-CC27 Chiou and Chen 2007
AF254453
AY303795-8 JE-CC27 Chiou and Chen 2007
AY303795-8 JE-CC27 Chiou and Chen 2007
AY303795-8 JE-CC27 Chiou and Chen 2007
AY303795-8 DV2 8 strains Wong et al 2007
Page 14 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
AJ556803–AJ556 DV2 8 strains Wong et al 2007
814
AJ556803–AJ556 DV2 8 strains Wong et al 2007
814
AJ556803–AJ556 DV2 8 strains Wong et al 2007
814
AJ556803–AJ556 TBE pTNd/c (replicon) Hoenninger et al 2008
814
U27495 TBE pTNd/c (replicon) Hoenninger et al 2008
U27495 TBE pTNd/c (replicon) Hoenninger et al 2008
U27495 TBE pTNd/c (replicon) Hoenninger et al 2008
U27495 TBE pTNd/c (replicon) Hoenninger et al 2008
U27495 TBE pTNd/c (replicon) Hoenninger et al 2008
U27495 TBE pTNd/c (replicon) Hoenninger et al 2008
U27495 TBE pTNd/c (replicon-9a) Hoenninger et al 2008
U27495 TBE pTNd/c (replicon-∆polyA) Hoenninger et al 2008
U27495 TBE pTNd/c (replicon-∆var) Hoenninger et al 2008
U27495 IRES-eGFP (Gehrke et. al 2005) (cassette) Hoenninger et al 2008
U27495 IRES-ME (Orlinger et. al 2006) (cassette) Hoenninger et al 2008
U27495 IRES-a771c and IRES-26a(Orlinger et. al 2007) Hoenninger et al 2008
(cassette)
U27495 DV2 Strain 16681 and its plasmid strain16681pst Sangiambut et al 2008
M84727,U87411, DV2 Strain 16681 and its plasmid strain16681pst Sangiambut et al 2008
or NC_001474
M84727,U87411, DV2 Strain 16681 and its plasmid strain16681pst Sangiambut et al 2008
or NC_001474
M84727,U87411, DV2 Strain 16681 and its plasmid strain16681pst Sangiambut et al 2008
or NC_001474
Page 15 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
M84727,U87411, DV2 Strain 16681 and its plasmid strain16681pst Sangiambut et al 2008
or NC_001474
M84727,U87411, DV4 Strain 814669 FRhL clone Lai et al 2007
or NC_001474
AF326573 DV4 Strain 814669 C6/36 clone Lai et al 2007
AF326573 TBE - pTd/bc Orlinger et al 2007
U27495 TBE - pTd/bc Orlinger et al 2007
U27495 TBE - pTd/bc Orlinger et al 2007
U27495 TBE - pTd/bc Orlinger et al 2007
U27495 TBE - pTd/bc Orlinger et al 2007
U27495 WNV replicon Rossi et al 2007
not identified WNV replicon Rossi et al 2007
not identified WNV replicon Rossi et al 2007
not identified WNV replicon Rossi et al. 2007
not identified WNV replicon Rossi et al. 2007
not identified WNV replicon Rossi et al. 2007
not identified WNV Evans and Seeger 2007
Page 16 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
not identified WNV replicon Evans and Seeger 2007
not identified WNII genome Evans and Seeger 2007
not identified WNV Jia et. Al 2007
EF657887 DV1 Bordignon et al 2007
AF226687
Page 17 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
Mutation (protein name) Natural/Artificial
Env-K307E Artificial ESM caused by nucleotid change in Egene
Env-K307E Artificial ESM caused by nucleotid change in Egene
NS1 E1114G Artificial M
NS2A M11581I Artificial M
NS2A T1321A Artificial M
NS3 L1602F Artificial M
NS3 S1632P Artificial M
NS3 D1865G Artificial M
NS5 N2583I Artificial M
NS5 E2664G Artificial M
NS5 I3362T Artificial M
NS5 K2924R Artificial M
E Protein Asp181Tyr Domain I Artificial ESM
E Protein Ala123Lys Domain II Artificial ESM
E Protein Gly368Arg Domain III Artificial ESM
E Protein L68P or F, E Protein S154N, E Protein Glycosylation at E-154-156 Natural Mutation – Early cell culture passage of WNI
E Protein S154N, Glycosylation NYS E-154-156 Natural Mutation – Recovered from mouse brain inoc w/ WNI-568
E Protein L68P, Y155N, Glycosylation at 155-157 NST Natural Mutation – mosquito passed strain of WNI
E Protein Y155N, K307E Glycosylation at E 155-157 NST Artificial ESM of WNI-25
E: V35A, K386N, R486K Artificial ESM
E: S169P ,G275R,F43K Artificial ESM
E Protein Lys388Asn, Asp390Asn Natural Mutation – obtained from clone of DEN2 Mexican strain
E Protein Asp390Asn Natural Mutation – obtained from clone of DEN2 Mexican strain
E Protein Asp390His Natural Mutation – obtained from clone of DEN2 Mexican strain
E Protein Asp390Asn Natural Mutation – obtained from clone of DEN2 Mexican strain
E Protein Asp390Asn Natural Mutation – obtained from clone of DEN2 Mexican strain
E Protein Asp390Asn Natural Mutation – obtained from clone of DEN2 Mexican strain
E Protein Asp390His Natural Mutation – obtained from clone of DEN2 Mexican strain
E Protein Asp390His Natural Mutation – obtained from clone of DEN2 Mexican strain
E Protein T69I Artificial ESM via Mab selecting
E Protein E71D Artificial ESM via Mab selecting
E Protein S112G Artificial ESM via Mab selecting
E Protein I124N Artificial ESM via Mab selecting
E Protein F279S Artificial ESM via Mab selecting
E Protein T293I Artificial ESM via Mab selecting
E Protein K307E Artificial ESM via Mab selecting
E Protein E311G Artificial ESM via Mab selecting
Page 18 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
E Protein Q52K or R Artificial ESM via Mab selecting
E Protein I126T Artificial ESM via Mab selecting
E Protein K136E Artificial ESM via Mab selecting
E Protein I270S Artificial ESM via Mab selecting
E Protein S275P Artificial ESM via Mab selecting
E Protein G333D Artificial ESM via Mab selecting
E Protein D308N Artificial ESM via Mab selecting
E Protein S310P Artificial ESM via Mab selecting
E Protein K311Q or N Artificial ESM via Mab selecting
E Protein A126E Artificial ESM via Mab selecting
E Protein R128S Artificial ESM via Mab selecting
E Protein F274V Artificial ESM via Mab selecting
E Protein S276R Artificial ESM via Mab selecting
silent nuc NS4B CA7129-7130UU Artificial ESM via Mab selecting
E Protein D67G Artificial ESM via Mab selecting
E Protein A71V Artificial ESM via Mab selecting
E Protein A123K Artificial ESM via Mab selecting
E Protein K171E Artificial ESM via Mab selecting
E Protein D181Y Artificial ESM via Mab selecting
E Protein Q233K Artificial ESM via Mab selecting
E Protein G368R Artificial ESM via Mab selecting
E Protein Y384H Artificial ESM via Mab selecting
E Protein S389R Artificial ESM via Mab selecting
E Protein N71K, Y, or H Artificial ESM via Mab selecting
E Protein D72G Artificial ESM via Mab selecting
E Protein M125I Artificial ESM via Mab selecting
E Protein D155G Artificial ESM via Mab selecting
E Protein T158I Artificial ESM via Mab selecting
E Protein Ala18Ser, Ala54Glu Artificial M via passaging through mouse brain
E Protein Phe277Ser Artificial M via passaging through mouse brain
E Protein Glu401Lys, Thr403Ile Artificial M via passaging through mouse brain
E Protein Thr266Ile, Ile268Thr Artificial M via passaging through vero cells
E Protein Phe191Val Artificial M via passaging through vero cells
E Protein Phe191Leu, Glu291Val Artificial M via passaging through vero cells
prM Lys26Gln, E Protein Phe191Leu, Lys202Arg, Ile268Val Artificial M via passaging through vero cells
Page 19 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
prM Lys26Thr, E Protein Ile268Ser Artificial M via passaging through vero cells
E Protein Phe191Leu, Lys202Arg Artificial M via passaging through vero cells
E Protein Thr155Ala; loss glycosylation site at E-133 Artificial M via passaging through Ae. albopictus cells
E Protein Thr155Met; loss glycosylation site at E-133 Artificial M via passaging through Ae. albopictus cells
NS2A Ala30Pro Artificial M via cloning replicon RNA w/ puromycin resistance, luciferase and
beta-galactosidase gene
NS2A Asn101Asp Artificial M via cloning replicon RNA w/ puromycin resistance, luciferase and
beta-galactosidase gene
NS5 Pro270Ser Artificial M via cloning replicon RNA w/ puromycin resistance, luciferase and
beta-galactosidase gene
NS4B Pro101Leu, Nuc C7129, silent nuc in NS4B C7359U, silent nuc in NS5 Artificial M via 5-Fu mutatgenesis of DEN4 virus
U9047C
NS4B Pro101Leu, NS4B nuc C7124U, silent nuc NS4B CA7129-7130UU and Artificial M via cloning Pro101Leu into rDEN4delta30 vaccine candidate
deletion in 3'-UTR from nuc 10478-10507
NS4B Pro101Leu, NS4B nuc C7124U, silent nuc NS4B U6521C and silent nuc Artificial M via cloning Pro101Leu into wt DEN4 cDNA
NS4B CA7129-7130UU
NS5 DR21-22AA Artificial M via Kunkel mutagenesis
NS5 RK22-23AA Artificial M via Kunkel mutagenesis
NS5 KE23-24AA Artificial M via Kunkel mutagenesis
NS5 EE26-27AA Artificial M via Kunkel mutagenesis
NS5 KD46-47AA Artificial M via Kunkel mutagenesis
NS5 EE157-158AA Artificial M via Kunkel mutagenesis
NS5 KH200-201AA Artificial M via Kunkel mutagenesis
NS5 RH246-247AA Artificial M via Kunkel mutagenesis
NS5 EK253-254AA Artificial M via Kunkel mutagenesis
NS5 KE356-357AA Artificial M via Kunkel mutagenesis
NS5 KK387-388AA Artificial M via Kunkel mutagenesis
NS5 KK388-389AA Artificial M via Kunkel mutagenesis
NS5 RE396-397AA Artificial M via Kunkel mutagenesis
NS5 EE397-398AA Artificial M via Kunkel mutagenesis
NS5 DK436-437AA Artificial M via Kunkel mutagenesis
NS5 RE500-501AA Artificial M via Kunkel mutagenesis
NS5 EE520-521AA Artificial M via Kunkel mutagenesis
NS5 DK523-524AA Artificial M via Kunkel mutagenesis
NS5 KK524-525AA Artificial M via Kunkel mutagenesis
NS5 KD525-526AA Artificial M via Kunkel mutagenesis
Page 20 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
NS5 KD596-597AA Artificial M via Kunkel mutagenesis
NS5 KE641-642AA Artificial M via Kunkel mutagenesis
NS5 ER642-643AA Artificial M via Kunkel mutagenesis
NS5 EK645-646AA Artificial M via Kunkel mutagenesis
NS5 KE649-650AA Artificial M via Kunkel mutagenesis
NS5 DR654-655AA Artificial M via Kunkel mutagenesis
NS5 RE750-751AA Artificial M via Kunkel mutagenesis
NS5 ED808-809AA Artificial M via Kunkel mutagenesis
NS5 ED820-821AA Artificial M via Kunkel mutagenesis
NS5 DK827-828AA Artificial M via Kunkel mutagenesis
NS5 KE877-878AA Artificial M via Kunkel mutagenesis
NS5 EE878-879AA Artificial M via Kunkel mutagenesis
NS5 KE23-24AA, KH200-201AA Artificial M via Kunkel mutagenesis
NS5 KE23-24AA, RE396-397AA Artificial M via Kunkel mutagenesis
NS3 S68D, nuc U4725G, NS3 S68D, nuc C4726A, deletion in 3'-UTR from nuc Artificial M, charge-to-alanine and point mutations previously done by site-
10478-10507 directed mutagenesis; chimeric clone created via cloning techniques
E Protein D225A, nuc A1612C, NS4B T102A, nuc A7131G, deletion in 3'-UTR Artificial M, charge-to-alanine and point mutations previously done by site-
from nuc 10478-10507 directed mutagenesis; chimeric clone created via cloning techniques
NS4B M48L, nuc A6969U, NS4B G119R, nuc G7182C, deletion in 3'-UTR from Artificial M, charge-to-alanine and point mutations previously done by site-
nuc 10478-10507 directed mutagenesis; chimeric clone created via cloning techniques
NS3 G103R, nuc G4830A, NS5 V1821, nuc G8106A, deletion in 3'-UTR from Artificial M, charge-to-alanine and point mutations previously done by site-
nuc 10478-10507 directed mutagenesis; chimeric clone created via cloning techniques
NS4B L112F, nuc A7163C, deletion in 3'-UTR from nuc 10478-10507 Artificial M, charge-to-alanine and point mutations previously done by site-
directed mutagenesis; chimeric clone created via cloning techniques
NS3 I1597T Artificial M via site directed mutagenesis
NS3 S1632P Artificial M via site directed mutagenesis
NS4B V2351A Artificial M via site directed mutagenesis
NS4B L2354S Artificial M via site directed mutagenesis
NS4B L2354F Artificial M via site directed mutagenesis
NS4B G2361S Artificial M via site directed mutagenesis
NS4B A2482V Artificial M via site directed mutagenesis
NS5 K2510R Artificial M via site directed mutagenesis
3'-UTR A > U Artificial M via site directed mutagenesis
3'-UTR A > U Artificial M via site directed mutagenesis
Page 21 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
NS3 I1597T, DEN2 structural genes, 3'-UTR deletion 10478-10507 Artificial M via cloning of previously site directed mutants into rDEN2/4delta30
chimeric virus
NS3 S1632P, DEN2 structural genes, 3'-UTR deletion 10478-10507 Artificial M via cloning of previously site directed mutants into rDEN2/4delta30
chimeric virus
NS4B V2351A, DEN2 structural genes, 3'-UTR deletion 10478-10507 Artificial M via cloning of previously site directed mutants into rDEN2/4delta30
chimeric virus
NS4B L2354S, DEN2 structural genes, 3'-UTR deletion 10478-10507 Artificial M via cloning of previously site directed mutants into rDEN2/4delta30
chimeric virus
NS4B L2354F, DEN2 structural genes, 3'-UTR deletion 10478-10507 Artificial M via cloning of previously site directed mutants into rDEN2/4delta30
chimeric virus
NS4B G2361S, DEN2 structural genes, 3'-UTR deletion 10478-10507 Artificial M via cloning of previously site directed mutants into rDEN2/4delta30
chimeric virus
NS4B A2482V, DEN2 structural genes, 3'-UTR deletion 10478-10507 Artificial M via cloning of previously site directed mutants into rDEN2/4delta30
chimeric virus
NS5 K2510R, DEN2 structural genes, 3'-UTR deletion 10478-10507 Artificial M via cloning of previously site directed mutants into rDEN2/4delta30
chimeric virus
3'-UTR A > U, DEN2 structural genes, 3'-UTR deletion 10478-10507 Artificial M via cloning of previously site directed mutants into rDEN2/4delta30
chimeric virus
3'-UTR A > U, DEN2 structural genes, 3'-UTR deletion 10478-10507 Artificial M via cloning of previously site directed mutants into rDEN2/4delta30
chimeric virus
Core Protein deletion from residues 39-44 Artificial M
Core Protein Gly42Ala Artificial M
Core Protein Gly42A, Pro43A Artificial M
incidental: prM T173M, nuc C612U, purposeful: 3'-SL sequence (nucleotide Artificial M generated by recombination between linearized prs424/DEN1 WP
mutations): deletion of A @ 7 and U @ 73 and U4A and C74U and pcr frament containing mutations
purposeful: 3'UTR deletion of nucleotides from 172 to 143, incidental: E protein Artificial M generated by recombination of pR424DEN1WP and linearized
T552S, nuc A1748U PCR product
deletion of 3'NC region from nucleotides 172-143 artificial introduced deletion mutations
deletion of 3'NC region from nucleotides 172-113 artificial introduced deletion mutations
deletion of 3'NC region from nucleotides 172-83 artificial introduced deletion mutations
deletion of 3'NC region from nucleotides 243-183 artificial introduced deletion mutations
deletion of 3'NC region from nucleotides 303-183 artificial introduced deletion mutations
Page 22 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
deletion of 3'NC region from nucleotides 333-183 artificial introduced deletion mutations
deletion of 3'NC region from nucleotides 384-183 artificial introduced deletion mutations
deletion of 3'NC region from nucleotides 172-113 and 384-183 artificial introduced deletion mutations
NS2A A30P Artifical M, substitution
Protein C deletion from AA 28-43 Artificial mutation – deletion via cloning
Protein C deletion from AA 28-46, P57L (nuc C302U) Artificial mutation – deletion via cloning
Protein C deletion from AA 28-48, Du78-85 (nuc Du364-387) Artificial mutation – deletion via cloning
Protein C deletion from AA 28-48, point mutation Q70L Artificial mutation – deletion cloning, point mutation via passaging
Protein C deletion from AA 28-48, duplication from I78 to L85 Artificial mutation – deletion via cloning, duplication via passaging
Protein C deletion from AA 28-48, T81M (nuc C374U) Artificial mutation – deletion cloning, duplication mutation via passaging
Protein C deletion from AA 28-48, Du59-K77 (nuc Du302-363) Artificial mutation – deletion cloning, point mutation via passaging
Protein C deletion from AA 28-48, T72I (nuc C347 U) Artificial mutation – deletion cloning, point mutation via passaging
Protein C deletion from AA 28-48, N56I, V66F, T72I (nuc A299U, G328U, Artificial mutation – deletion cloning, point mutation via passaging
C347U)
Protein C deletion from AA 28-48, V66F, T81M (nuc G328U, C374U) Artificial mutation – deletion cloning, point mutation via passaging
Protein C deletion from AA 28-54, K79I (nuc A368U) Artificial mutation – deletion cloning, point mutation via passaging
Protein C deletion from AA 28-54, T81M (nuc C374U) Artificial mutation – deletion cloning, point mutation via passaging
Protein C deletion from AA 28-54, Q90L (nuc A401U) Artificial mutation – deletion cloning, point mutation via passaging
Protein C deletion from AA 28-57, Duplications 24-27 and 58-78 (nuc Artificial mutation – deletion cloning, duplication mutation via passaging
Duplications 202-213 and 304-366)
Protein C deletion from AA 28-57, K79I (nuc A368U) Artificial mutation – deletion cloning, point mutation via passaging
Protein C deletion from AA 28-54 Artificial mutation – deletion via cloning
Protein C deletion from AA 28-57 Artificial mutation – deletion via cloning
Page 23 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
Protein C deletion from AA 28-46 Artificial mutation – deletion via cloning
Protein C deletion from AA 28-48 Artificial mutation – deletion via cloning
prm G15S, E E311G Artificial ESM – passage in BHK-21 in presence of DEN2 specific Mab 6B2
E Protein P53S, E71D, S112G, I124N, F402F/L Artificial M – passage control
prM G15S, E Protein T69I, E71D, S112G, I124N, F402L Artificial ESM – passage in BHK-21 in presence of DEN2 specific Mab 10F2
E Protein P53S, S112G, I124N, F402L Artificial M – passage control
NS2A/B cleavage site, QKT->QST (AAG->TCG) Artifical M, substitution via cloning
NS2A/B cleavage site, QKT->QKV (ACT->GTT) Artificial M, substitution
NS2A/B cleavage site, QKT->QQT (AAG->CAG) Artificial M, substitution
NS2A/B cleavage site, QKT->QET (AAG->GAG) Artifical M, substitution
NS2A/B cleavage site, QKT->QRT (AAG->AGG) Artifical M, substitution
NS2A/B cleavage site, QKT->QIT (AAG->ATC) Artifical M, substitution
NS2A/B cleavage site, QKT->SKT (CAG->TCG) Artifical M, substitution
NS2A/B cleavage site, QKT->RRS (CAG-AAG-ACT->AGG-AGG-AGT) Artifical M, substitution
NS2A/B cleavage site, QST->QKLEEGST Artifical M, substitution
NS2A/B cleavage site, QIT->QKRETIT Artifical M, substitution
NS2A/B cleavage site, QST->QRRSTGST Artifical M, substitution
NS2A/B cleavage site, QKT->SKT, NS3 D343V Artifical M, substitution
NS2A/B cleavage site, QKT->SKT , NS3 D343A Artifical M, substitution
NS2A/B cleavage site, QKT->SKT, NS3 D343G Artifical M, substitution
NS3 D343V Artifical M, substitution
NS3 D343A Artifical M, substitution
NS3 D343G Artifical M, substitution
NS1 silent mutation, no AA changes; nuc: AAGC2845-2848CTCA, T3076C, Artifical M, oligonucleotide-directed mutagenesis, substitution
G3079T, A3082C
NS1 S132A, AGC2846-2848GCT Artifical M, oligonucleotide-directed mutagenesis, substitution
NS1 N130A, AA2840-2841GC Artifical M, oligonucleotide-directed mutagenesis, substitution
NS1 T210A, A3080G, A3082C Artifical M, oligonucleotide-directed mutagenesis, substitution
Page 24 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
NS1 N208A, AA3074-3075GC Artifical M, oligonucleotide-directed mutagenesis, substitution
NS1 S132A, T210A, AGC2846-2848GCT, A3080G, A3082C Artifical M, oligonucleotide-directed mutagenesis, substitution
NS1 N130A, N208A, AA2840-2841GC, AA3074-3075GC Artifical M, oligonucleotide-directed mutagenesis, substitution
NS3: E17A/E19A/D20A Artifical M, charge to alanine substitution
NS3 G32A/ Y33A Artifical M, charge to alanine substitution
NS3 K63A/ R64A/E66A, Artifical M, charge to alanine substitution
NS3 V95A/Q96A Artifical M, charge to alanine substitution
NS3 E179A/D180A/ D181A Artifical M, charge to alanine substitution
NS5 methyltransferase: S56T, S56A Artificial mutations
NS5 methyltransferase: W87I Artificial mutations
NS5 methyltransferase: W87K Artificial mutations
Page 25 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
NS5 methyltransferase: W87Y Artificial mutations
NS5 methyltransferase: D131A Artificial mutations
NS5 methyltransferase: D131E Artificial mutations
NS5 methyltransferase: D131N Artificial mutations
NS5 methyltransferase: K76A/D79A Artificial mutations
NS5 methyltransferase: D79A/L80I Artificial mutations
NS5 methyltransferase: G81A/G83A/G85A Artificial mutations
NS5 methyltransferase: D146A/E149A Artificial mutations
NS5 methyltransferase: G48A, G48P Artificial mutations
NS5 methyltransferase: K46A/R47A/E49A Artificial mutations
NS5 methyltransferase: E138A/K139A/D141A Artificial mutations
NS5 methyltransferase: E192A/K193A/E195A Artificial mutations
NS5 methyltransferase: K61T Artificial mutations
NS5 methyltransferase: K61Q Artificial mutations
NS5 methyltransferase: D146S Artificial mutations
NS5 methyltransferase: D146L Artificial mutations
NS5 methyltransferase: D146P Artificial mutations
NS5 methyltransferase: D146R Artificial mutations
NS5 methyltransferase: D146T Artificial mutations
NS5 RNA dependent RNA polymerase: W751R Artificial mutations
NS1: P138L Artificial mutations
5' UTR: U38-ins Artificial mutations
5' UTR: G35U Artificial mutations
Page 26 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
Env- domain III (residues 305, 326, and 380) Neuroadapted viruses compared
NS2A: I59N artificial
NS2A: T149P artificial
NS2A: I59R artificial
NS2A: I59V artificial
NS2A: K198S artificial
NS2A: I59Y artificial
NS2A: I59S artificial
NS2A: I59T artificial
NS5 artificial
5' A artificial
5'-3' A artificial
5' B artificial
5'-3' B artificial
5' UAR 1 artificial
5' UAR 2 artificial
5' UAR 3 artificial
5' UAR 4 artificial
5' UAR 5 artificial
5' UAR 6 artificial
5' UAR 7 artificial
3' UAR 1 artificial
3' UAR 2 artificial
3' UAR 3 artificial
3' UAR 4 artificial
3' UAR 5 artificial
3' UAR 6 artificial
3' UAR 7 artificial
5'-3' UAR 1 artificial
5'-3' UAR 2 artificial
Page 27 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
5'-3' UAR 3 artificial
5'-3' UAR 4 artificial
5'-3' UAR 5 artificial
5'-3' UAR 6 artificial
5'-3' UAR 7 artificial
NS1: N130A artificial
NS1: N130A/N207A artificial
NS1: N207A artificial
E: Y155N, Y155S artificial
5' UAR 1 (replicon) artificial
5' UAR 2 (replicon) artificial
5' UAR 3 (replicon) artificial
5' UAR 4 (replicon) artificial
5' UAR 5 (replicon) artificial
5' UAR 6 (replicon) artificial
5' UAR 1 (genome) artificial
5' UAR 2 (genome) artificial
5' UAR 3 (genome) artificial
5' UAR 4 (genome) artificial
5' UAR 5 (genome) artificial
5' UAR 6 (genome) artificial
NS4B: C102S natural
NS4B: E249G natural
NS4B: A79T natural
Walker A motif of Helicase: G199A, K200A, T201A artificial
Walker A motif of Helicase: K200R, K200Q, K200N, K200D, K200E, K200H artificial
Motif IV: R461A, R464A artificial
Motif IV: Q457A,R458A artificial
Motif IV: R459A, G460A,V462A, and G463A artificial
Page 28 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
NS3: Q341A/ T342A/D343A, D343V artificial
NS3: E338A/D339A, I334A/P345A/S346A, H353A/D354A artificial
NS3: E347A/P348A/W349A, W349A/N350A artificial
NS3: E347A, P348A,W349A, N350A artificial
NS3: W349F, W349Y, W349H artificial
NS3: W349Q, W349L, W349K artificial
SIN-NS2B3: S138A, R461Q artificial
3'UTR (already include deleted nucleotides 173-143) 50 deletions artificial
3'UTR (already include deleted nucleotides 173-143) 61 deletions artificial
3'UTR (already include deleted nucleotides 173-143) 80 deletions artificial
3'UTR (already include deleted nucleotides 173-143) 86 deletions artificial
3'UTR (already include deleted nucleotides 173-143) 116A deletions artificial
3'UTR (already include deleted nucleotides 173-143) 116B deletions artificial
3'UTR (already include deleted nucleotides 173-143) 146 deletions artificial
3'UTR (already include deleted nucleotides 173-143)/ 31 deletions artificial
3'UTR 31 deletions artificial
NS5-3' : rDEN3-3'UTR-D4 artificial
NS5-3' : rDEN3-3'UTR-D4(with 30nt deletions) artificial
5'CS and 3'CS in C protein coding region all A-U switched to U-A artificial
Page 29 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
5'CS and 3'CS in C protein coding region all G-C switched to C-G artificial
5'CS and 3'CS in C protein coding region all A-U switched to G-C artificial
5'CS and 3'CS in C protein coding region reverse sequences artificial
5'CS and 3'CS in C protein coding region reverse complimentary sequences artificial
single-nucleotide substitutions in CS both 5' and 3' regions (terminal ends), m1 artificial
and m2
single-nucleotide substitutions in CS both 5' and 3' regions, m4 and m7 artificial
single-nucleotide substitutions in CS both 5' and 3' regions, m3,m8,m10,m11 artificial
single-nucleotide substitutions in CS both 5' and 3' regions, m5, m6 artificial
single-nucleotide substitutions in CS both 5' and 3' regions, m9 artificial
5' UTR m1 insertion artificial
5' UTR m2 insertion artificial
3' UTR m1 insertion artificial
3' UTR m2 insertion artificial
double-nucleotide substitutions in CS both 5' and 3' regions,m4 and m7 artificial
combination
double-nucleotide substitutions in CS both 5' and 3' regions,m4 and m7 artificial
combination in whole viral genome
5'CS double-nucleotide substitution of m4/m7, 3'CS double-nucleotide artificial
substitution of m4/m7
5'CS double-nucleotide substitution of m4/m7, 3'CS double-nucleotide artificial
substitution of m4/m8
E138glu/ NS4A162leu (L1variant) natural - substitution occurred in transfection
E138lys/NS4A162Ile (S1variant) natural - substitution occurred in transfection
E306glu (L3variant) natural - substitution occurred in transfection
E306lys (S5variant) natural - substitution occurred in transfection
E306glu (L4variant) natural - substitution occurred in transfection
E306lys (S1variant) natural - substitution occurred in transfection
E36asn/E135ser/E389asp (L1variant) natural - substitution occurred in transfection
E36ser/E135ser/E389asp (L3variant) natural - substitution occurred in transfection
E36ser/E135ser/E389asn (S6variant) natural - substitution occurred in transfection
E36asn/E135Ile/E389asp (S8variant) natural - substitution occurred in transfection
E: G385A natural- one outbreak to another
Page 30 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
NS1: nucleotide changes natural- one outbreak to another
NS1: nucleotide changes natural- one outbreak to another
NS1: A815G natural- one outbreak to another
C17rluc reporter (first 17 aa of the capsid plus renilla luciferase, rest of prM and artificial
E except for TM2 deleted)
C27rluc reporter (first 27 aa of the capsid plus renilla luciferase, rest of prM and artificial
E except for TM2 deleted)
C37rluc reporter (first 37 aa of the capsid plus renilla luciferase, rest of prM and artificial
E except for TM2 deleted)
C17fluc reporter (first 17 aa of the capsid plus fire fly luciferase, rest of prM and artificial
E except for TM2 deleted)
C17fluc-FMDV2A reporter (first 17 aa of the capsid plus firefly luciferase, rest of artificial
prM and E except for TM2 deleted) 2A from foot and mouth disease
C17fluc-TaV2A reporter (first 17 aa of the capsid plus firefly luciferase, rest of artificial
prM and E except for TM2 deleted) 2A from Thosea asigna
NS5:GDD-GAA artificial
all but 9 adenines of 49 removed from poly A tract of 3' NCR artificial
all adenines of 49 removed from poly A tract of 3' NCR artificial
entire variable region removed of 3' NCR artificial
enhanced green fluorescent protein under control of an EMCV IRES cloned into artificial
C17fluc-TaV2A
encodes for the TBEV prM and E proteins under control of an EMCV IRES artificial
cloned into C17fluc-TaV2A
A771C substitution in oligo(A) loop/insertion of 19 additional adenines in the artificial
same oligo(A) loop cloned into C17fluc-TaV2A
C:K6A/K7A artificial
C:K73A/K74A artificial
C:R85A/K86A artificial
C:R97A/R98A artificial
Page 31 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
C:R85A/K86A, R97A/R98A artificial
DENV4v3 A-G mutation at nucleotide 1458 natural - 3 cycles of neutralization and propagation
DENV4v4 C-T mutation at nucleotide 1465 natural - 3 cycles of neutralization and propagation
pTBEV-bc was created from Taking TBEV and removing the prM and E regions artificial
and inserting with a EMCV IRES in the 3'NCR - E: D308A, A317T
mutant clones of TBEV-bc E: D308A/A317T natural after passage of pTBEV-bc
mutation in IRES : consistent with nucleotide 771 of the EMCV genome A-C natural after passage of pTBEV-bc
mutation in IRES:consistent with nucleotide 771 of the EMCV genome A-C and natural after passage of pTBEV-bc
E: D308A/A317T
mutation in IRES : U769A/poly(A), caused insertion of multiple Adenines natural after passage of pTBEV-bc
(between 11-35)
NS3: 117K artificial
NS4B: E249G artificial
NS5: P528H artificial
NS2A: D73H artificial
NS2A: M108K artificial
NS2A: A30P artificial
NS4B: E34A/K35A,E45A/E46A, R74A/K75A, E121A/K123A,D35A/R37A, artificial
E132A/R135A, E163A/R164A
Page 32 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
NS4B: E22A/K24A artificial
NS4B: E22A/K24A artificial
NS2A: V61A, prM: P54S natural-variant in cell culture
E: T276P natural after passage in cell culture
Page 33 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
Phenotype
rendered antibody G8D11unable to bind to the glycoprotein E in
radioimmunoprecipitation therefore allowing for replication
rendered antibody G8D11unable to bind to the glycoprotein E in
radioimmunoprecipitation therefore allowing for replication
attenuation & temperature sens.
attenuation & temperature sens.
attenuation & temperature sens.
attenuation & temperature sens.
attenuation & temperature sens.
attenuation & temperature sens.
attenuation & temperature sens.
attenuation & temperature sens.
attenuation & temperature sens.
temperature sens. NOT attenuated
no diff from wild in ts or plaque size. was attenuated.more sens. to ph
(conform stab)
smaller plaques, not ts. attenuated. more sens. to ph (conform stab)
ts, normal plaque. attenuated. more sens. to ph (conform stab)
Neuroinvasive and Neurovirulent
Neuroinvasive and Neurovirulent
Loss Neuroinvasiveness, still neurovirulent
Loss Neuroinvasiveness, still Neurovirulent
Less fusion of cells, failure to agglutinate erythrocytes, smaller plaques
Produced small lytic plaque, Medium neurovirulence, var. mortality (10 to 7th viral
titer(increased from parental strain); decreased pH fusion threshhold -0.2
P6-P10, severe hindlimb paralysis; 100% mortality; >10 to 7th viral
titer(increased from parental strain); decreased pH fusion threshhold -0.7
P6-P10, severe hindlimb paralysis; 100% mortality; >10 to 7th viral
titer(increased from parental strain); decreased pH fusion threshhold -0.6 to -
0.8
P6-10 had 0.5-2 x 10 to 7th viral titers (10-100 fold higher); larger forming
plaques earlier in time(3 days as opposed to 6 days)
P6-10 had 0.5-2 x 10 to 7th viral titers (10-100 fold higher); larger forming
plaques earlier in time(3 days as opposed to 6 days); decreased pH fusion
threshhold -0.8 to -1.0
P6-10 had 0.5-2 x 10 to 7th viral titers (10-100 fold higher); larger forming
plaques earlier in time(3 days as opposed to 6 days)
P6-10 had 0.5-2 x 10 to 7th viral titers (10-100 fold higher); larger forming
plaques earlier in time(3 days as opposed to 6 days)
Page 35 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
P6-10 had 0.5-2 x 10 to 7th viral titers (10-100 fold higher); larger forming
plaques earlier in time(3 days as opposed to 6 days); decreased pH fusion
threshhold -0.6 to -0.8
P6-10 had 0.5-2 x 10 to 7th viral titers (10-100 fold higher); larger forming
plaques earlier in time(3 days as opposed to 6 days); decreased pH fusion
threshhold -0.6 to -0.8
smaller plaque produced at 7 days; extensive syncytium formation at 5-6
days; increased pH fusion threshhold +0.4
smaller plaque produced at 7 days; extensive syncytium formation at 5-6
days; increased pH fusion threshhold +0.4
no change in initiation of RNA synthesis (72% of wt) in BHK, 17 fold increase
in RNA in BHK, 50x increase in colonies in human(HEK293/HEp-2); did not
inhibit IFN-beta driven transcription
decrease in initiation of RNA synthesis (55% of wt) in BHK, 13 fold increase
in RNA synthesis in BHK; 20x increase in hunan(HEK293/HEp-2)
decrease in initiation of RNA synthesis (12% of wt) in BHK, 1.8 fold increase
in RNA synthesis in BHK
decreased plaque size in C6/36 cells but increased plaque size in Vero/HuH7
cells; low percentage of total infection in Ae. agyptis and no dissemination; no
infection in mosquito heads; not ts in vero/HuH7 or decreased replication in
mice; increased rep w/ SCID/HuH7 mice
smaller plaque size in C6/36, increased plaque size in Vero/HuH7 cells; high
percentage total infection but no dissemination; no ts in Vero/HuH7 and no
change in replication in mice; mild decrease in replication in SCID/HuH7 mice
small plaque size in C6/36, increased plaque size in Vero/HuH7; low total
infection and no dissemination; decreased infection in head to 25% in
Toxorhynchites splendens; no ts in Vero/HuH7, no change in replication in
mice; increased replication in SCID/HuH7 mice
not ts, no attenuation
ts in Vero & HuH7, attenuated replication in suckling mice
ts in HuH7, attenuated replication in suckling mice
ts in Vero & HuH7, no attenuation
not ts, no attenuation
ts in HuH7, attenuated replication in suckling mice
ts in HuH7
not ts, no attenuation
not ts, no attenuation
ts in HuH7, attenuated replication in suckling mice
ts in Vero & HuH7, attenuated replication in suckling mice
ts in Vero & HuH7, no attenuation
ts in HuH7, no attenuation
ts in Vero & HuH7, no attenuation
ts in Vero & HuH7, attenuated replication in suckling mice
ts in Vero & HuH7, no attenuation
ts in Vero & HuH7, no attenuation
ts in HuH7, no attenuation
not ts, attenuated replication in suckling mice
not ts, attenuated replication in suckling mice
Page 36 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
ts in Vero & HuH7, no attenuation
not ts, no attenuation
ts in Vero & HuH7, attenuated replication in suckling mice
ts in Vero , no attenuation
not ts, no attenuation
ts in Vero & HuH7, attenuated replication in suckling mice
not ts, no attenuation
ts in Vero & HuH7, attenuated replication in suckling mice
ts in Vero & HuH7, no attenuation
ts in HuH7, attenuated replication in suckling mice
not ts, attenuated replication in suckling mice
not ts, attenuated replication in suckling mice
ts in Vero & HuH7, no attenuation
ts in Vero & HuH7, attenuated replication in suckling mice
significant decrease in viral titer in SCID/HuH7 mice, slight decrease in viral
titer in rhesus monkeys, protected monkey against DEN4 challenge
slight decrease in viral titer in SCID/HuH7, significant decrease in viral titer in
rhesus monkeys, protected monkey against DEN4 challenge
mild decrease in viral titer in SCID/HuH7, mild decrease in viral titer in rhesus
monkeys, protected monkey against DEN4 challenge
significant decrease in viral titer in SCID/HuH7 mice compared to delta30
alone, no decrease compared to charge-to-alanine, significant decrease in
viral titer in rhesus monkeys, protected monkey against DEN4 challenge
significant decrease in viral titer in SCID/HuH7 mice compared to delta30 &
charge-to-alanine, significant decrease in viral titer in rhesus monkeys,
protected monkey against DEN4 challenge
increased plaque size in Vero cells, attenuated replication in mouse brain
increased plaque size in Vero cells, attenuated replication in mouse brain
increased plaque size in Vero cells, no attenuation of replication in mouse
brain
increased plaque size in Vero cells, no attenuation of replication in mouse
brain
increased plaque size in Vero cells, no attenuation of replication in mouse
brain
increased plaque size in Vero cells, no attenuation of replication in mouse
brain
increased plaque size in Vero cells, no attenuation of replication in mouse
brain
increased plaque size in Vero cells, no attenuation of replication in mouse
brain
no increase in plaque size in Vero cells
no increase in plaque size in Vero cells
Page 37 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
substantial increase in replication in Vero cells
substantial increase in replication in Vero cells
substantial increase in replication in Vero cells
substantial increase in replication in Vero cells
substantial increase in replication in Vero cells
substantial increase in replication in Vero cells
substantial increase in replication in Vero cells
substantial increase in replication in Vero cells
substantial increase in replication in Vero cells
substantial increase in replication in Vero cells
core protein only localized in cytoplasm, was not present in nucleus
core protein did not colocalize with nucleolin, distributed as filamentous
strands in nucleus, found in cytoplasm also
core protein was not transported into nucleus, only in cytoplasm, smaller
infectious plaque, decreased release of infectious particles, increased release
of defective particles, impaired RNA replication in Vero cells, earlier peak of
protein synthesis, imaired neuroinvasiveness
mild decrease in viral titers in rhesus monkeys, lower Ab titers than wt, but
still generated protective immunity
less than 1 day viremic and low viral titers (0.8 log 10 PFU), lower Ab titers
relative to wt but still generated protective immunity, decreased viral
replication by 100 fold in HuH-7 mice, highly infective in T. splendens
(approach log of 1.0 concentration after intrathoracic injection)
1-10 faint plaques, plaques similar to wt DEN4, 9 mm(C6/36 cells), late and
faint plaque production(LLC-MK2 cells @ 9 days), reduced Ab titers relative
to wt
1-10 faint plaques, plaques similar to wt DEN4, 10 mm(C6/36 cells), no
plaque @ 6 days, faint plaques at 9 days(LLC-MK2 cells), high Ab titers
against protein E
no plaques produced(LLC-MK2 or C6/36), no RNA present (lethal mutation)
not studied due to mutations not being stable after cell passage
20-30 faint plaques, smaller plaque than wt, 6 mm(C6/36 cells), late and faint
plaque production(LLC-MK2 cells), high Ab titers against protein E and NS1
Page 38 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
RNA present via IFA, smaller plaque than wt, 5mm(C6/36 cells), late and faint
plaque production, present at 9 days(LLC-MK2 cells), poor Ab titer response
no plaques produced(LLC-MK2), RNA present via IFA, smaller plaque than
wt, 3mm(C6/36 cells), no plaque(LLC-MK2 cells), poor Ab titer response
no plaques produced(LLC-MK2), RNA present via IFA, smaller plaque than
wt, 3mm(C6/36 cells)
higher IFN-beta produced in Hep2 cells infected w/ SFV, abortive replication
of WNV-Kun in A549 cells, smaller plaque foci on A549 cells, decreased viral
titers in A549 cells, more IFN-alpha/beta produced in mice, higly attenuated
in mice(lower virulence), protected from challenge w/ WNV-NY99
infection of BHK-21 w/o mouse passaging; infection similar to wt
increased plaque size in BHK-21 cells
restored ability of virus to infect BHK-21 cells
infection of BHK-21 w/o mouse passaging, reduced and delayed release of
viral particles in corneal endothelial cells, atten index (LD/ID) > 10 to 5 in
mice
infection of BHK-21 w/o mouse passaging, reduced and delayed release of
viral particles in corneal endothelial cells, atten index (LD/ID) > 10 to 5 in
mice
restored ability of virus to infect BHK-21 cells
restored ability of virus to infect BHK-21 cells
restored ability of virus to infect BHK-21 cells
restored ability of virus to infect BHK-21 cells
restored ability of virus to infect BHK-21 cells
restored ability of virus to infect BHK-21 cells
restored ability of virus to infect BHK-21 cells
restored ability of virus to infect BHK-21 cells
restored ability of virus to infect BHK-21 cells
restored ability of virus to infect BHK-21 cells
inability of virus to infect BHK-21 cells
inability of virus to infect BHK-21 cells
Page 39 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
reduced ability of virus to infect BHK-21 cells
inability of virus to infect BHK-21 cells
lower absorbance, lower fusion, decrease in titer due to 42 C of approx 3
PFU/ml
lower absorbance, normal fusion, decrease in titer due to 42C of approx 4
PFU/ml
decrease in absorbance, normal fusion, decrease in titer due to 42C by
approx 5 PFU/ml
decrease in absorbance, normal fusion, decrease in titer due to 42C by
approx 3 PFU/ml
no plaque produced, no infectious particles produced (lacks capsid and RNA,
still has E and protein), plaque production restored with trans NS1-2A
small plaque formation with infectivity similar to wild type
no plaque formation
no plaque formation
plaque formation and infectivity similar to wild type
no plaque formation
no plaque formation
plaque formation and infectivity similar to wild type, cleavage of NS2Aalpha
more efficient than wild type
plaque formation and infectivity similar to wild type
plaque formation and infectivity similar to wild type
smaller plaque formation, infectivity similar to wild type
plaque formation with infectivity similar to wild type
plaque formation and infectivity similar to wild type
plaque formation and infectivity similar to wild type
larger plaque formation than wild type, infectivity similar to wild type
larger plaque formation than wild type, infectivity similar to wild type
larger plaque formation than wild type, infectivity similar to wild type
phenotypically identical to wild type
small plaque, lower virus yield, delayed cytopathological effects, faster
migration in gel than wt, slight decrease in protein production, reduced RNA
production up to 24 hrs postinf., attenuation in mice (16% mortality with mild
illnesses in survivors)
small plaque, lower virus yield, delayed cytopathological effects, faster
migration in gel than wt, slight decrease in protein production, reduced RNA
production up to 24 hrs postinf., attenuation in mice (16% mortality with mild
illnesses in survivors)
medium plaque(smaller than wt), wt level viral yields, cytopathological effects
similar to wt(24-48hrs postinf), faster migration than wt in gel, similar levels of
RNA accumulation in wt, similar virulence and phenotype in mice
Page 40 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
medium plaque(smaller than wt), wt level viral yields, cytopathological effects
similar to wt(24-48hrs postinf), faster migration than wt in gel, similar levels of
RNA accumulation in wt, similar virulence and phenotype in mice
tiny plaque, lower viral yields, slower migration than wt on gel, lower protein
production, reduced RNA production up to 24 hrs postinf, attenuation in
mice(no deaths and minimal signs of disease)
tiny plaque, lower viral yields, slower migration than wt on gel, lower protein
production, reduced RNA production up to 24 hrs postinf, attenuation in
mice(no deaths and minimal signs of disease)
interaction between NS2B/NS3 retained, no severe inhibition of proteinase
activity
interaction between NS2B/NS3 retained, low titres recovered (ts), probable
restriction of replication
interaction between NS2B/NS3 retained, no severe inhibition of proteinase
activity, reduced plaque size, titer comprable to wild type, initial lag in virus
release, no temp. sensitivity observed
reduction of intereaction between NS2B/NS3 observed, low titres recovered
(ts),probable restriction of replication
interaction between NS2B/NS3 retained, no severe inhibition of proteinase
activity, reduced plaque size, titer comprable to wild type, initial lag in virus
release, no temp. sensitivity observed
Both changes cause loss of N7 metransferase, S56T has 100% 2' Ome
activity. No growth.
Loss of both N7 metransferase and 2' Ome activity. No Growth.
Loss of both N7 metransferase and 2' Ome activity. No Growth.
Page 41 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
Loss of both N7 metransferase and 2' Ome activity. Temperature sensitive
growth.
Loss of both N7 metransferase and 2' Ome activity. No Growth.
100 % N7 metransferase activity and loss of 2' Ome activity. Temperature
sensitive growth.
Loss of both N7 metransferase and 2' Ome activity. Temperature sensitive
growth.
Loss of both N7 metransferase and 2' Ome activity. No Growth.
Loss of both N7 metransferase and 2' Ome activity. No Growth.
Loss of both N7 metransferase and 2' Ome activity. No Growth.
Loss of both N7 metransferase and 2' Ome activity. No Growth.
Loss of both N7 metransferase and 2' Ome activity. G48A has temperatures
sensitive growth, G48P no growth.
loss of 2' Ome activity. Temperature sensitive growth.
enhanced activity in both N7metransferase and 2' Ome. enhanced growth at
higher temperatures.
enhanced activity in 2'Ome. Growth only at lower temperature.
contributes to the rescue of viral replication of D146S mutation by improving
N7 methylation activity
contributes to the rescue of viral replication of D146S mutation by improving
N7 methylation activity
produces virus, some N7 methylation activity retained, no 2' Ome activity
produces no virus, no N7 methylation activity retained, no 2' Ome activity
produces no virus, no N7 methylation activity retained, no 2' Ome activity
produces no virus, no N7 methylation activity retained, no 2' Ome activity
some N7 methylation activity retained, no 2' Ome activity
contributes to the rescue of viral replication of D146S mutation, improves
polymerase activity
does not contribute to the rescue of viral replication of D146S mutation
contributes to the rescue of viral replication of D146S mutation, do not
increase cap methylations
contributes to the rescue of viral replication of D146S mutation, do not
increase cap methylations
Page 42 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
Determined these 3 residues were critical for neuroinvasiveness
loss of RNA replication, low VLP production with reversion
rescues the defect in I59N (compensatory), allows for virus
assembly/secretion
severely impaired RNA replication, low VLP production with reversion to I59Y
enhanced RNA replication, no effect on VLP production
loss of RNA replication, no effect on VLP production
enhanced RNA replication, no effect on VLP production
enhanced RNA replication, no effect on VLP production
enhanced RNA replication, no effect on VLP production
reduced luciferase activity, RNA synthesis probably impaired
luciferase activity similar to WT, suggests efficient synthesis, however this is
time sensitive, after 96 h. activity is severly reduced and no replication occurs
luciferase activity similar to WT, suggests efficient synthesis
reduced luciferase activity, no RNA synthesis
reduced luciferase activity, no RNA synthesis
maintains base pairs, able to replicate
disrupted hybridization, reduced RNA replication
hybridization occurred, mismatch present, replication still occurred
disrupted hybridization, reduced RNA replication
disrupted hybridization, reduced RNA replication
disrupted hybridization, reduced RNA replication
no replication detected
hybridization disrupted, no RNA replication
generated stem loop mismatch,disrupted hybridization, reduced RNA
replication
hybridization occurred, mismatch present in stem loop , replication still
occurred
efficient RNA replication
reduced RNA replication
reduced RNA replication
no replication detected
restores replication capability defected in 3'UAR mut.
restored some RNA replication lost in 5' and 3' UAR mut., reduction of
synthesis probably due to a mismatch at position -8
Page 43 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
high levels of RNA replication
high levels of RNA replication
high levels of RNA replication
high levels of RNA replication
no replication detected
no infectious viral particles found after one passage blocks the transition of
WT In trans.
no infectious viral particles found after one passage
infectious viral particles found after one passage
may destabilize doman I/II interface leading to attenuation
forms stable duplex with 3'UAR,viral translation occurs, replication occurs
forms stable duplex with 3'UAR,viral translation occurs, replication occurs
forms stable duplex with 3'UAR,viral translation occurs, replication occurs
does not form stable duplex with 3'UAR, viral translation occurs, replication
does not occur
forms stable duplex with 3'UAR,viral translation occurs, replication does not
occur
forms stable duplex with 3'UAR,viral translation occurs, replication occurs
formed p.f.u. ,exhibited immunofluorescence, no adaptive change in
transfected virus
formed p.f.u. ,exhibited immunofluorescence, no adaptive change in
transfected virus
formed p.f.u. ,exhibited immunofluorescence, no adaptive change in
transfected virus
no p.f.u. formed, exhibited some delayed immunofluorescence may indicate
reversion,adaptation made which led to rescue of replication in replicon
formed pinpoint p.f.u.,exhibited delayed immunofluorescence, adaptation
increased efficiency of replication and infectivity
formed pinpoint p.f.u. exhibited delayed immunofluorescence, no adaptive
change in transfected virus
temperature sens. At 41°C, attenuation in mice
reduced RNA synthesis in host cells
may alter the hydrophobicity of NS4B
all lost ATPase and helicase activity, no infectious virus recovered upon
transfection
all lost ATPase and helicase activity
complete loss of ATPase activity and helicase activity,no infectious virus
recovered upon transfection
loss of most ATPase activity and helicase activity,no infectious virus
recovered upon transfection
ATPase and helicase activity conserved, G460A produced viable infectious
virus
Page 44 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
produced WT plaques 72 h.p.t., retained WT luciferase activity, retained
packaging efficiency
produced small plaques 72 h.p.t.,loss of luciferase activity except for
H353A/D354A which retained WT levels, reduced packaging efficiency in all
produced no plaques 72 h.p.t., retained WT luciferase activity,no packaging
efficiency observed
all but W349A produced plaques at 72 h.p.t., all retained WT luciferase
activity, packaging efficiency observed in all but W349A, W349A blocks
production of infectious virus particles, but not the non-infectious particles
all but W349H produced plaques, W349H produced no plauqes, all retained
WT luciferase activity, packaging efficiency was conserved in all but W349H
All produced no plaques, all retained WT luciferase activity, no packaging
efficiency was conserved
previously known to inhibit enzymatic activity, did not effect -trans
complementation in W349A, enzymatic activity deemed unneeded
recovered in cDNA clones in C6/36cells ,viable, but replication restricted in
Vero cells
recovered in cDNA clones in C6/36cells
recovered in cDNA clones in C6/36cells
recovered in cDNA clones in C6/36cells , restricted in replication in SCID-
HuH-7 mice more than 10 fold, in Vero replicated like WT, In C6/36 replicated
10 fold lower than WT,in vero contained a coding change in M, and a single
nt substitution in the 3' UTR, also a mixed pop. found at NS5 stop that coded
for 2 extra amino acids, not detected in rhesus, but did infect
recovered in cDNA clones in C6/36cells ,viable, but replication restricted in
Vero cells
recovered in cDNA clones in C6/36cells ,deemed unstable due to natural
mutation of 8nt deletion and a single substitution of A→G at nt265
recovered in cDNA clones in C6/36cells ,viable, but replication restricted in
Vero cells
recovered in cDNA clones in C6/36cells , restricted in replication in SCID-
HuH-7 mice a bit less than 10 fold , in Vero replicated like WT, no replication
in C6/36 cells, in vero contained a single NS4B coding change, not detected
in rhesus but did infect, infects Toxorynchites but is attenuated
recovered in cDNA clones in C6/36cells , also recovered in Vero cells,
deemed unstable due to natural mutaion of 25nt deletion
in vero replicated nearly 100 fold higher than WT, in C6/36 WT replication
observed, detected in 75% of inoculated rhesus monkeys (suggests that ∆30
is necessary for attenuation
restricted in replication in SCID-HuH-7 mice more than 10 fold, in Vero
replicated like WT, in C6/36 replicatd 10 fold lower than WT, in vero
contained a 3'UTR substitution, not detected in rhesus but did infect
no luciferase activity at 48h post transfection
Page 45 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
no luciferase activity at 48h post transfection
no luciferase activity at 48h post transfection
no luciferase activity at 48h post transfection
no luciferase activity at 48h post transfection
showed drastic reduction of RNA replication
no detectable reduction in RNA replication (WT)
showed greater than 50% reduction in RNA replication
showed about a 20% reduction in RNA replication
showed about a 30% reduction in RNA replication
showed drastic reduction of RNA replication
replicated much better than m2, suggests A at position 2 in 3'CS is critical for
RNA replication
showed drastic reduction of RNA replication
showed drastic reduction of RNA replication
no detectable reduction in RNA replication (WT), no interference with genome
packaging, no reduction in foci forming effectiveness
no detectable defect despite 5' and 3' CS mutations and amino acid changes
no detectable RNA replication at 48 hours
10,000 times less efficent at producing foci fomation than WT at 48h, but 4
day incubation produced viable replicons
virus growth faster than the S1 variant
growth titer increased after one passage greater than that of LP growth
signifying that Neuro-2a cells prefer small plaque variants, more efficient
inhibition with heparin, survival times longer in mice
higher neurovirulence than the S5 variant
higher neurovirulence than the S1 variant, virus growth faster than S1 variant
growth titer increased after one passage greater than that of LP growth
signifying that Neuro-2a cells prefer small plaque variants, more efficient
inhibition with heparin
higher neurovirulence than S6/S8 variants
higher neurovirulence than S6/S8 variants
growth titer increased after one passage greater than that of LP growth
signifying that Neuro-2a cells prefer small plaque variants, more efficient
inhibition with heparin, slower virus growth than LP variants, lowest growth
titer of four variants
growth titer increased after one passage greater than that of LP growth
signifying that Neuro-2a cells prefer small plaque variants, survival times
longer in mice, slower virus growth than LP variants
caused a change in the viral genome of the second outbreak V129I,
happened at B-cell reactive regions, this could change the presentation of the
epitope producing different antibodies
Page 46 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
caused T349A, happened at B-cell reactive regions
caused T351A, happened at B-cell reactive regions
caused a change in the viral genome of the second outbreak K272R,
happened at B-cell reactive regions
initial input RNA translated , no replication in BHK cells, no detectable NS1
protein
initial input RNA translated, then decrease in activity followed by increase
again (biphasic)
initial input RNA translated, then decrease in activity followed by increase
again (biphasic)
initial input RNA translated, then decrease in activity followed by increase
again (biphasic)
activity highter than in C17fluc, suggests more efficient release of fluc at the
2A site versus 2B site in C17fluc
activity highter than in C17fluc-FMDV2A, suggests more efficient release of
fluc at the 2A site versus 2B site in C17fluc
abolishes viral RNA replication, but not translation
did not significantly affect the efficiency of cap-dependent translation, does
not affect RNA replication
did not significantly affect the efficiency of cap-dependent translation, does
not affect RNA replication
slight decrease in efficiency of cap-dependent translation, does not effect
RNA replication
no strong affect on the efficiency of cap-dependent translation, eventually
displayed reduced luciferase activity than parental replicon, replication delay
no strong affect on the efficiency of cap-dependent translation, eventually
displayed reduced luciferase activity than parental replicon, replication delay
did not demonstrate significanly increased efficiency of input RNA, increase
as compared to IRES ME suggesting positive effect on RNA replication
efficiency
initial high nucleolar staining, but large decrease after 72 h, nuclear
localization affected by time only in PS cells, reduced replication in C6/36
gained additional substitution mutation A6V in mammal cells
staining reduced significantly from parent cells, but appeared in 80%+ cells,
no increase in nucleoplasmic staining, found less frequently in Vero cells,
reduced replication in C6/36, gained additional point mutation at C317A
resulting in a A73N and A74N in later days
staining reduced significantly from parent cells, but appeared in 80%+ cells,
no increase in nucleoplasmic staining, found less frequently in Vero cells,
reduced replication in C6/36
initial high nucleolar staining, but large decrease after 72 h, nuclear
localization affected by time only in PS cells, not viable in vero cells, reduced
replication in C6/36
Page 47 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
not viable
resulted in E174K substitution in the E protein, could not be neutralized by
IgG5H2∆D plaque growth on vero cells similar to FRhL parent strain ,
mutation did not hinder growth , substitution reduced antibody binding affinity
resulted in L176P substitution in the E protein , somewhat neutralized by
IgG5H2∆D, plaque growth on vero cells similar to C6/36 parent strain,
mutation did not hinder growth, substitution reduced antibody binding affinity
virus is viable but replicates much slower than WT
produced more infectious particles than original bc, better specific infectivity
than original bc
produced more infectious particles than original bc, produced more RNA than
original BC but less than wildtype, greater specific infectivity than original bc
produced more infectious particles than original bc, titer equal to that of WT,
greatest increase in specific infectivity
still functional, efficiency varies with respect to number of adenines,
moderate increase in expression from the cap-dependent cistron, no strong
effect on E protein expression
noncytopathic, High Colony Formation efficiency, reduced replication and
decreased staining , reverted to WT when introduced to a NS1-5 ET2AN
replicon or genome
exhibited WT phenotype
exhibited WT phenotype
100% colony-forming efficiency, antigen staining less intense than WT
suggesting reduced WNR replication, weak expression of eGFP fluroescence
, infected Huh7 cells appeared healthy and dividing but were antigen positive,
produced smaller antigen positive foci than WT in vero cells, very little CPE
after 72hpi, not virulent in mice, IFN response delayed and deceased
compared to WT
100% colony-forming efficiency, antigen staining less intense than WT
suggesting reduced WNR replication, weak expression of eGFP fluroescence
,produced smaller antigen positive foci than WT in vero cells, very little CPE
after 72hpi, not virulent in mice
3.5% colony-forming efficiency, WT antigen staining efficiency, WT eGFP
fluroescence intensity, infected Huh7 cells appeared moribund like WT and
were antigen positive, produced somewhat smaller antigen postive foci than
WT but larger than other two NS2A mutations, CPE readily evident after
72hpi, virulent to mice and showed no reversion to WT
did not show competent RNA replication
Page 48 aaa8a56d-9ebb-4ce6-8e8e-af81155136db.xls
greater than 95% postive for beta-lactamase showed replication, produced
colonies after 3 weeks of selection in G418, demonstrated WT NS4B
replication and translation these results were not cell specific,IFN- signaling
pathway proved to remain functional in host cell , allowed for more stat1
phosphorylation than WT but overall stat1 protein was decreased from
parental cells, allowed for some induction of ISG
greater than 95% postive for beta-lactamase showed replication, produced
colonies after 3 weeks of selection in G418, demonstrated WT NS4B
replication and translation these results were not cell specific, IFN stimulation
completely inhibited, completely blocked STAT1 phosphorylation,caused less
cell death than WT
smaller plaques,somewhat ts at 41C, attenuative in mice, lower replication
efficiency, lower infection rate of C. pipens, may have a defect blocking cell-
cell spread, reversion occurred in vivo
extra information
Virus name Reference Protein/Residue/Region Location
DEN2 Wong et al 2007 E: 129 Domain II
DEN2 Wong et al 2007 NSI n/a
TBEV Hoenninger et al 2008 Internal Poly (A) tract 3' NCR
TBEV Hoenninger et al 2008 TM2 E protein
TBEV Hoenninger et al 2008 mutations IRES
DV2 Sangiambut et al 2008 C n/a
TBEV Orlinger et al 2007 E/ IRES n/a
TBEV Orlinger et al 2008 E: E387K n/a
TBEV Orlinger et al 2009 E: D308A n/a
WNV Rossi et al 2007 NS2A n/a
WNV/KUNV Rossi et al 2007 NS2A n/a
Page 49
extra information
Associated Amino Acid
usually either I or V , ( I for DV1, V for DV3, and L for DV4)
n/a
n/a
n/a
n/a
n/a
n/a
Glutamate
Asparagine
n/a
A30P mutation
Page 50
extra information
Significance/Important Information
important for type specific neutralizing antibodies, amino acid specific probably for importance of E protein function
stimulates cytotoxic T-Cell responses
no impact on translation or replication in mammal cells when removed or truncated
serves as an internal signal sequence for establishing the proper topology of the polyprotein in the ER membrane
as previously hypothesized, mutations causing weaker binding of the ribosome do not increase the fitness of bicistronic RNA
nucleolar localization not needed for dengue virus replication
mutations in these reason seemed to be sole reason for titer increases after passage
when aa is changed, result is alteration of surface charge
when aa is changed, result is alteration of surface charge, increases affinity of virus binding to cell surface
important for the establishment of noncytopathic persistent replication in mammalian cells
not the same between strains of North American/Australian variety, likely unsuitable for an attenuated vaccine strain
Page 51
extra information
tance of E protein function
tein in the ER membrane
crease the fitness of bicistronic RNA
ing to cell surface
an attenuated vaccine strain
Page 52
NS2A
D00246 KUN Liu et al. 2004 NS2A Ala30Pro
NS2A1/MRM
61C
D00246 KUN Liu et al. 2004 NS2A
NS2A2/MRM Asn101Asp
61C
NC_001563 WNV, Kunjin Liu et al., 2006 NS2A A30P
strain
NC_002031 YF NS2Alpha Kummerer and NS2A/B
QKV Rice, 2002 cleavage site,
QKT->QKV
(ACT->GTT)
NC_002031 YF NS2Alpha Kummerer and NS2A/B
QQT Rice, 2002 cleavage site,
QKT->QQT
(AAG->CAG)
NC_002031 YF NS2Aalpha Kummerer and NS2A/B
QET Rice, 2002 cleavage site,
QKT->QET
(AAG->GAG)
NC_002031 YF NS2Aalpha Kummerer and NS2A/B
QRT Rice, 2002 cleavage site,
QKT->QRT
(AAG->AGG)
NC_002031 YF NS2Aalpha Kummerer and NS2A/B
QIT Rice, 2002 cleavage site,
QKT->QIT (AAG-
>ATC)
NC_002031 YF NS2Aalpha Kummerer and NS2A/B
SKT Rice, 2002 cleavage site,
QKT->SKT
(CAG->TCG)
NC_002031 YF NS2Aalpha Kummerer and NS2A/B
RRS Rice, 2002 cleavage site,
QKT->RRS
(CAG-AAG-ACT-
>AGG-AGG-
AGT)
NC_002031 YF NS2Aalpha Kummerer and NS2A/B
KLEEG Rice, 2002 cleavage site,
reconstructed QST-
mutant >QKLEEGST
NC_002031 YF NS2Aalpha Kummerer and NS2A/B
KRET Rice, 2002 cleavage site,
reconstructed QIT->QKRETIT
mutant
NC_002031 YF NS2Aalpha Kummerer and NS2A/B
RRSTG Rice, 2002 cleavage site,
reconstructed QST-
mutant >QRRSTGST
NC_002031 YF NS2Aalpha Kummerer and NS2A/B
SKT D343V Rice, 2002 cleavage site,
double mutant QKT->SKT, NS3
D343V
Page 53
NS2A
NC_002031 YF NS2Aalpha Kummerer and NS2A/B
SKT D343A Rice, 2002 cleavage site,
double mutant QKT->SKT ,
NS3 D343A
NC_002031 YF NS2Aalpha Kummerer and NS2A/B
SKT D343G Rice, 2002 cleavage site,
double mutant QKT->SKT, NS3
D343G
AY274504 or KUN Leung et al 2008 NS2A: I59N
D00246
AY274504 or KUN Leung et al 2008 NS2A: T149P
D00246
AY274504 or KUN Leung et al 2008 NS2A: I59R
D00246
AY274504 or KUN Leung et al 2008 NS2A: I59V
D00246
AY274504 or KUN Leung et al 2008 NS2A: K198S
D00246
AY274504 or KUN Leung et al 2008 NS2A: I59Y
D00246
AY274504 or KUN Leung et al 2008 NS2A: I59S
D00246
AY274504 or KUN Leung et al 2008 NS2A: I59T
D00246
not identified WNV Rossi et al. 2007 NS2A: D73H
not identified WNV Rossi et al. 2007 NS2A: M108K
not identified WNV Rossi et al. 2007 NS2A: A30P
Page 54
NS2A
Artificial M via cloning replicon RNA w/ puromycin resistance,
luciferase and beta-galactosidase gene
Artificial M via cloning replicon RNA w/ puromycin resistance,
luciferase and beta-galactosidase gene
Artifical M, substitution
Artificial M, substitution
Artificial M, substitution
Artifical M, substitution
Artifical M, substitution
Artifical M, substitution
Artifical M, substitution
Artifical M, substitution
Artifical M, substitution
Artifical M, substitution
Artifical M, substitution
Artifical M, substitution
Page 55
NS2A
Artifical M, substitution
Artifical M, substitution
artificial
artificial
artificial
artificial
artificial
artificial
artificial
artificial
artificial
artificial
artificial
Page 56
NS2A
no change in initiation of RNA synthesis (72% of wt) in BHK, 17 fold increase
in RNA in BHK, 50x increase in colonies in human(HEK293/HEp-2); did not
inhibit IFN-beta driven transcription
decrease in initiation of RNA synthesis (55% of wt) in BHK, 13 fold increase in
RNA synthesis in BHK; 20x increase in hunan(HEK293/HEp-2)
higher IFN-beta produced in Hep2 cells infected w/ SFV, abortive replication
of WNV-Kun in A549 cells, smaller plaque foci on A549 cells, decreased viral
titers in A549 cells, more IFN-alpha/beta produced in mice, higly attenuated in
mice(lower virulence), protected from challenge w/ WNV-NY99
small plaque formation with infectivity similar to wild type
no plaque formation
no plaque formation
plaque formation and infectivity similar to wild type
no plaque formation
no plaque formation
plaque formation and infectivity similar to wild type, cleavage of NS2Aalpha
more efficient than wild type
plaque formation and infectivity similar to wild type
plaque formation and infectivity similar to wild type
smaller plaque formation, infectivity similar to wild type
plaque formation with infectivity similar to wild type
Page 57
NS2A
plaque formation and infectivity similar to wild type
plaque formation and infectivity similar to wild type
loss of RNA replication, low VLP production with reversion
rescues the defect in I59N (compensatory), allows for virus
assembly/secretion
severely impaired RNA replication, low VLP production with reversion to I59Y
enhanced RNA replication, no effect on VLP production
loss of RNA replication, no effect on VLP production
enhanced RNA replication, no effect on VLP production
enhanced RNA replication, no effect on VLP production
enhanced RNA replication, no effect on VLP production
100% colony-forming efficiency, antigen staining less intense than WT
suggesting reduced WNR replication, weak expression of eGFP fluroescence
, infected Huh7 cells appeared healthy and dividing but were antigen positive,
produced smaller antigen positive foci than WT in vero cells, very little CPE
after 72hpi, not virulent in mice, IFN response delayed and deceased
compared to WT
100% colony-forming efficiency, antigen staining less intense than WT
suggesting reduced WNR replication, weak expression of eGFP fluroescence
,produced smaller antigen positive foci than WT in vero cells, very little CPE
after 72hpi, not virulent in mice
3.5% colony-forming efficiency, WT antigen staining efficiency, WT eGFP
fluroescence intensity, infected Huh7 cells appeared moribund like WT and
were antigen positive, produced somewhat smaller antigen postive foci than
WT but larger than other two NS2A mutations, CPE readily evident after
72hpi, virulent to mice and showed no reversion to WT
Page 58