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Herpes Viruses


									Influenza Virus
Gus Kousoulas, Ph.D.

                  Common Properties
                    myxo- mucous tropic

•   orthomyxovirus = influenza

•    (-) polarity ssRNA
•    enveloped viruses
•    encapsidates RNA polymerase
•    causes worldwide disease
•    responsible for > 10% work/school absence
•    acute infections and diseases
•    known since 1500’s
        Orthomyxovirus: classification

Three types

•  Influenza A - highly variable
  - infects humans, birds, pigs, horses, seals
  - most prevalent human virus
  - cause of most human epidemics
• Influenza B - infects only animals
• Influenza C - infects human and swine
    - antigenic stable, only mild illness
                       Avian Influenza
•   Avian influenza is an infectious disease of birds caused by type A strains of
    the influenza virus.

•   Infection causes a wide spectrum of symptoms in birds, ranging from mild
    illness to a highly contagious and rapidly fatal disease resulting in severe
    epidemics. The latter is known as “highly pathogenic avian influenza”. This
    form is characterized by sudden onset, severe illness, and rapid death, with a
    mortality that can approach 100%.

•   To date, all outbreaks of the highly pathogenic form have been caused by
    influenza A viruses of subtypes H5 and H7.

•   Avian influenza viruses do not normally infect species other than birds and
    pigs. The first documented infection of humans with an avian influenza virus
    occurred in Hong Kong in 1997, when the H5N1 strain caused severe
    respiratory disease in 18 humans, of whom 6 died.
                      Avian Influenza

•   An outbreak of highly pathogenic H7N7 avian influenza, which began
    in the Netherlands in February 2003, caused the death of one
    veterinarian two months later, and mild illness in 83 other humans.

•   In January 2004, laboratory tests confirmed the presence of H5N1
    avian influenza virus in human cases of severe respiratory disease in
    the northern part of Viet Nam.

•   Recently, virulent asian influenza strains were detected in dead
    chickens and specimens of young patients that died from influenza-
    related complications (Turkey).

•   Based on historical patterns, influenza pandemics can be expected to
    occur, on average, three to four times each century when new virus
    subtypes emerge and are readily transmitted from person to person.
    In the 20th century, the great influenza pandemic of 1918–1919,
    which caused an estimated 40 to 50 million deaths worldwide, was
    followed by pandemics in 1957–1958 and 1968–1969.
                      Diagram of influenza virus

Genome- segmented RNA

Capsid- nucleoprotein

Nucleocapsid- helical

Matrix proteins- 1, 2


Glycoproteins- NA, HA

Structural proteins

Non-structural proteins
    Structure: viral components

• Hemagglutinin (HA) *
   - HA0 cleaved to become HA1, HA2
   - Naturally occurs as trimer
   - Sialic acid is cellular receptor
   - Responsible for membrane fusion
• Neuraminidase (NA)*
   - naturally occurs as tetramer
   - cleaves sialic acid at exit/egress
         Orthomyxovirus: Classification

• How to name an influenza virus?

 Type ABC/ City/ strain #/ year isolated/glycoproteins
                 HA(1-14)             NA (1-9)
        e.g. A/ HongKong/ 03/ 1968/ H3N2

• Worldwide epidemics = pandemics
   - 1918-19 influenza pandemic caused 20 million deaths
   - 1947, 1957 (Asian flu); 1968, 1977, 1987
 Portal of
 Entry of

Inhalation of
       Influenza virus genetic variation
  Antigenic drift
  . point mutations in RNA encoding HA or NA
  . results in new antigenic sites
  . occurs frequently- yearly changes
  . no correction for errors made by viral RNA polymerase
  . allows virus to avoid mucosal IgA antibodies

  Antigenic shift
. reassortment when two influenza strains infect the same cell
  e.g. avian and human virus infect same cell
. cause of periodic new influenza epidemics
. completely new set of HA and NA can be in progeny virus
. pandemics occurs typically every 10-14 years
Influenza virus variation


    Impact of Influenza Pandemics
• 1918-19 Spanish Flu (H1N1)
     • 20 to 40 million deaths worldwide
     • At least 550,000 US deaths (only 80% of
       pop. included in vital statistics data)
• 1957-58 Asian Flu (H2N2)
     • ~70,000 US deaths
• 1968-69 Hong Kong Flu (H3N2)
     • ~34,000 US deaths
• Current interpandemic influenza
     • ~36,000 US deaths
     • >200,000 hospitalizations
• "Bird Flu" Similar to Deadly 1918 Flu, Gene Study Finds
• Brian Handwerk
  for National Geographic News

• October 5, 2005
• Scientists have reconstructed the genetic code of the deadly
  1918 "Spanish flu," which swept the globe and killed an
  estimated 20 to 40 million people. Among their findings: The
  1918 virus strain developed in birds and was similar to the
  "bird flu" that today has spurred fears of another worldwide
        Influenza control and prevention
Yearly vaccine available- inactivated virus
 . ~70% protective for a given year
Current vaccine made in chicken embryo
        . cocktail of circulating human strains from previous
        . purify and formalin inactivate virus
        . each dose =10 billion virus particles
        . takes time to prepare
        . given in one dose before flu season
New vaccine options
 . HA and NA subunit (~15 μg of HA)
 . “cold adapted” live attenuated virus (Flu-Mist)
        (UM SPH Dr. Masaab), FDA approved
     Influenza control and prevention

• Who should receive vaccine?
   – Health care workers
   – High risk individuals
     . elderly > 65 years
     . people with underlying diseases
       (chronic lung disease, asthma,
       diabetes, heart disease)

   Current conventional vaccines will not
    protect against avian virulent strains!!!

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