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Epstein-Barr virus
Epstein-Barr virus
Epstein-Barr
causes infectious mononucleosis 35% to 65% of the time.
History
EBV is named after Anthony Epstein and Yvonne Barr, who together with Bert Achong,[2] discovered the virus in 1964 in cells cultured from the tumor specimens sent to them from Mulago Hospital in Kampala, Uganda by Denis Burkitt.[3] Burkitt and Epstein had met three years earlier in London during a talk by Burkitt on his findings regarding children’s cancers in tropical Africa. In the talk, Burkitt postulated that there may be an infectious component to what he referred to as "African Lymphoma". After the presentation, the two men met and Burkitt agreed to send Epstein frozen specimens for him to analyze.[4] Epstein, Barr and Achong were working as a team at the Middlesex Hospital at the time.
Two Epstein-Barr virions
Virus classification Group: Family: Subfamily: Genus: Species: Group I (dsDNA) Herpesviridae Gammaherpesvirinae Lymphocryptovirus Human herpesvirus 4 (HHV-4)
The Epstein-Barr Virus (EBV), also called Human herpesvirus 4 (HHV-4), is a virus of the herpes family (which includes Herpes simplex virus), and is one of the most common viruses in humans. Most people become infected with EBV, which is often asymptomatic but infection commonly causes infectious mononucleosis (also known as glandular fever). Epstein-Barr virus occurs worldwide. Most people become infected with EBV sometime during their lives, and therefore gain adaptive immunity, preventing repeated sickness from re-infection through EBV antibodies. [1] In the United States, as many as 95% of adults between 35 and 40 years of age have been infected. Infants become susceptible to EBV as soon as maternal antibody protection (present at birth) disappears. Many children become infected with EBV, and these infections usually cause no symptoms or are indistinguishable from the other mild, brief illnesses of childhood. In the United States and in other developed countries, many persons are not infected with EBV in their childhood years. When infection with EBV occurs during adolescence or young adulthood, it
Virology
The virus can execute many distinct programs of gene expression which can be broadly categorized as being lytic cycle or latent cycle. • The lytic cycle or productive infection results in staged expression of several viral proteins with the ultimate objective of producing infectious virions. Formally, this phase of infection does not inevitably lead to lysis of the host cell as EBV virions are produced by budding from the infected cell. Lytic proteins include gp350 and gp110.[5] • The latent cycle (lysogenic) programs are those that do not result in production of virions. A very limited, distinct set of viral proteins are produced during latent cycle infection. These include Epstein-Barr nuclear antigen (EBNA)-1, EBNA-2, EBNA-3A, EBNA-3B, EBNA-3C, EBNAleader protein (EBNA-LP) and latent membrane proteins (LMP)-1, LMP-2A and LMP-2B and the Epstein-Barr encoded RNAs (EBERs). In addition, EBV codes for
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From Wikipedia, the free encyclopedia
at least twenty microRNAs which are expressed in latently infected cells.[6]
Epstein-Barr virus
the virus presumably persists. Eventually, when host immunity develops, the virus persists by turning off most (or possibly all) of its genes, only occasionally reactivating to produce fresh virions. A balance is eventually struck between occasional viral reactivation and host immune surveillance removing cells that activate viral gene expression. The site of persistence of EBV may be bone marrow. EBV-positive patients who have had their own bone marrow replaced with bone marrow from an EBV-negative donor are found to be EBV-negative after transplantation.[8]
Programs
From studies of EBV gene expression in cultured Burkitt’s lymphoma cell lines, at least three programs exist: • EBNA1 only (group I) • EBNA1 + EBNA2 (group II) • Latent cycle proteins (group III) It is also postulated that a program exists in which all viral protein expression is shut off.
Latent cycle
Epstein-Barr virus and its sister virus KSHV can be maintained and manipulated in the laboratory in continual latency. While many viruses are assumed to have this property during infection of their natural host, they do not have an easily managed system for studying this part of the viral lifecycle. Further, Walter Henle and Gertrude Henle[1], together with Harald zur Hausen who later discovered the papillomaviruses[2] causing cervical cancer, discovered that EBV can directly immortalize B cells after infection, mimicking some forms of EBV-related neoplasia[3]. On infecting the B-lymphocyte, the linear virus genome circularizes and the virus subsequently persists within the cell as an episome.
Latent antigens
All EBV nuclear proteins are produced by alternative splicing of a transcript starting at either the Cp or Wp promoters at the left end of the genome (in the conventional nomenclature). The genes are ordered EBNA-LP/ EBNA-2/EBNA-3A/EBNA-3B/EBNA-3C/ EBNA-1 within the genome. The initiation codon of the EBNA-LP coding region is created by an alternate splice of the nuclear protein transcript. In the absence of this initiation codon, EBNA-2/EBNA-3A/ EBNA-3B/EBNA-3C/EBNA-1 will be expressed depending on which of these genes is alternatively spliced into the transcript.
Protein/genes Surface receptors
The Epstein-Barr Virus surface glycoprotein H (gH) is essential for penetration of B cells but also plays a role in attachment of virus to epithelial cells. [9] In laboratory and animal trials in 2000, it was shown that both antagonism of RA-mediated growth inhibition and promotion of LCL proliferation were efficiently reversed by the glucocorticoid receptor (GR) antagonist RU486.[10]
Transformation
When EBV infects B-lymphocytes in vitro, lymphoblastoid cell lines eventually emerge that are capable of indefinite growth. The growth transformation of these cell lines is the consequence of viral protein expression. EBNA-2, EBNA-3C and LMP-1 are essential for transformation while EBNA-LP and the EBERs are not. The EBNA-1 protein is essential for maintenance of the virus genome.[7] It is postulated that following natural infection with EBV, the virus executes some or all of its repertoire of gene expression programs to establish a persistent infection. Given the initial absence of host immunity, the lytic cycle produces large amounts of virus to infect other (presumably) B-lymphocytes within the host. The latent programs reprogram and subvert infected B-lymphocytes to proliferate and bring infected cells to the sites at which
References
[1] http://www.umm.edu/altmed/articles/ mononucleosis-000109.htm [2] "NIHERST: Caribbean Icons in STI". http://caribbean-icons.org/science/bertachong.htm. Retrieved on 2008-10-05. [3] Epstein MA, Achong BG, Barr YM (March 1964). "Virus particles in cultured lymphoblasts from Burkitt’s lymphoma".
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From Wikipedia, the free encyclopedia
Protein/ Stage gene/ antigen Description
Epstein-Barr virus
EBNA-1 latent+lytic EBNA-1 protein binds to a replication origin (oriP) within the viral genome and mediates replication and partitioning of the episome during division of the host cell. It is the only viral protein expressed during group I latency. EBNA-2 latent+lytic EBNA-2 is the main viral transactivator. EBNA-3 latent+lytic These genes also bind the host RBP-Jκ protein. LMP-1 LMP-2 EBER latent latent latent LMP-1 is a six-span transmembrane protein that is also essential for EBV-mediated growth transformation. LMP-2A/LMP-2B are transmembrane proteins that act to block tyrosine kinase signaling. EBER-1/EBER-2 are small nuclear RNAs of an unknown role. EBV microRNAs are encoded by two transcripts, one set in the BART gene and one set near the BHRF1 cluster. The three BHRF1 miRNAS are expressed during type III latency while the large cluster of BART miRNAs (up to 20 miRNAs) are expressed during type II latency. The functions of these miRNAs are currently unknown. early antigen membrane antigen viral capsid antigen
miRNAs latent
EBV-EA EBVVCA
lytic lytic
EBV-MA lytic
[4]
[5]
[6]
[7]
[8]
Lancet 1 (7335): 702–3. doi:10.1016/ S0140-6736(64)91524-7. PMID 14107961. Coakley D (2006). "Denis Burkitt and his contribution to haematology/oncology". Br J Haematol 135 (1): 17–25. doi:10.1111/j.1365-2141.2006.06267.x. PMID 16939495. Lockey TD, Zhan X, Surman S, Sample CE, Hurwitz JL (2008). "Epstein-Barr virus vaccine development: a lytic and latent protein cocktail". Front. Biosci. 13: 5916–27. PMID 18508632. http://www.bioscience.org/2008/v13/af/ 3126/fulltext.htm. The nomenclature used here is that of the Kieff lab. Other laboratories use different nomenclatures. Yates JL, Warren N, Sugden B (1985). "Stable replication of plasmids derived from Epstein-Barr virus in various mammalian cells". Nature 313 (6005): 812–5. doi:10.1038/313812a0. PMID 2983224. Gratama JW, Oosterveer MA, Zwaan FE, Lepoutre J, Klein G, Ernberg I (1988). "Eradication of Epstein-Barr virus by allogeneic bone marrow transplantation:
implications for sites of viral latency". Proc. Natl. Acad. Sci. U.S.A. 85 (22): 8693–6. doi:10.1073/pnas.85.22.8693. PMID 2847171. [9] Molesworth SJ, Lake CM, Borza CM, Turk SM, Hutt-Fletcher LM (July 2000). "Epstein-Barr virus gH is essential for penetration of B cells but also plays a role in attachment of virus to epithelial cells". Journal of virology 74 (14): 6324–32. doi:10.1128/ JVI.74.14.6324-6332.2000. PMID 10864642. PMC: 112138. http://jvi.asm.org/cgi/ pmidlookup?view=long&pmid=10864642. [10] Quaia M, Zancai P, Cariati R, Rizzo S, Boiocchi M, Dolcetti R (July 2000). "Glucocorticoids promote the proliferation and antagonize the retinoic acid-mediated growth suppression of Epstein-Barr virus-immortalized B lymphocytes". Blood 96 (2): 711–8. PMID 10887139. http://www.bloodjournal.org/ cgi/ pmidlookup?view=long&pmid=10887139.
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From Wikipedia, the free encyclopedia
Epstein-Barr virus
and the Abramson Comprehensive Cancer Center, University of Pennsylvania Medical School, Philadelphia, Pennsylvania 19104, USA • International Association for Research on EBV Body that organizes the two-yearly EBV research meeting. • Caribbean Icons, org Burt Achong
External links
• Epstein-Barr Virus: Implicated in Cancer Etiology in China, Impetus for a Vaccine Article in The Scientist 13(6):1, Mar. 15, 1999 (registration required) • National (USA) Center for Infectious Diseases website on EBV • Epstein Barr Virus Editor: Erle S. Robertson Department of Microbiology
Retrieved from "http://en.wikipedia.org/wiki/Epstein-Barr_virus" Categories: Herpesviruses, IARC Group 1 carcinogens This page was last modified on 20 May 2009, at 21:19 (UTC). All text is available under the terms of the GNU Free Documentation License. (See Copyrights for details.) Wikipedia® is a registered trademark of the Wikimedia Foundation, Inc., a U.S. registered 501(c)(3) taxdeductible nonprofit charity. Privacy policy About Wikipedia Disclaimers
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