Virology 23 Orthomyxoviruses*
Terms
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- Explain why an Orthomyxovirus genome should be a character on Grand Theft Auto
- Enveloped virus with 8 negative sense RNA genome segments that replicates in the nucleus and steals host 5’ capped termini of cellular mRNAs as primers for viral mRNA transcription
- What is the function of the Orthomyxovirus protein HA?
- HA, the hemagglutin (vaccine target) binds to sialic acid (N-acetyl neuraminic acid) present on cell surface molecules
- What is the function of the Orthomyxovirus protein M2?
- M2 is a tetrameric integral membrane protein which forms an ion channel (target of anti-influenza drugs amantidine and rimantadine)
- What are the types of influenza virus and how do they differ?
- Influenza type A, B, and C (contain different M and NP antigens and have different RNA sequences at the ends of their genome sequences)
- Who are the hosts of Influenza A?
- Influenza A: humans, birds, horses, pigs, etc. (large reservoir in animals). Cause flu epidemics
- Who are the hosts of Influenza B?
- Influenza B: humans
- Which Influenza causes epidemics?
- Influenza A causes epidemics
- Why are endosomes relevant to Orthomyxovirus replication?
- Low pH in endosomes stimulates conformational change of HA glycoprotein and causes fusion of viral envelope with endosome membrane
- What is Antigenic Shift
- A drastic change of multiple antigenic domains of HA or NA in an influenza virus, often associated with pandemics. Occurs as a result of the segmented genome of flu virus and the re-assortment of the viral genomes in the large animal reservoirs of the virus (unique to Influenza A because it is maintained in large animal reservoirs)
- What is Antigenic Drift
- Random process that occurs as a consequence of the mutations introduced by the viral RNA dependent RNA polymerase during replication
- What is the special problem of “Original antigenic sin?â€
- The immune response to the first infection with a virus having a dominating influence on subsequent immune responses
- Why is effective vaccination against flu difficult?
- Antigenic drift and antigenic shift render vaccination against flu difficult
- What are two drugs are used in anti-influenza A therapy?
- Amantadine and Rimantidine
- What do Amantadine and Rimantidine target?
- The M2 ion channel responsible for the alteration of pH required for viral uncoating and assembly
- What are two recently approved neuraminidase inhibitors that can inhibit both influenza A & B viruses?
- Relenza and Tamiflu
- What is the pathogenesis of primary influenza infection
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Short incubation period
No viremia
Interferons and cytokines cause fever, aches, edema
Stimulation of antibodies and virus-specific T cells
Immunity to re-infection mediated by IgA in respiratory tract - What are some of the complications of influenza
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Primary influenza pneumonia
Secondary bacterial pneumonia
Encephalitis, pericarditis, myositis
Reye's syndrome (children given aspirin are at increased risk for this syndrome)
Parkinson's?
Guillain-Barre? - What is the basic structure of the Orthomyxoviruses
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Large Enveloped RNA virus
SS negative RNA with 8 separate segments
Envelope derived from host cell membranes which contain viral glycoproteins HA and NA
Helical nucleocapsid - What promotes release of Orthomyxoviruses from the cell
- NA, the neuraminidase
- During Orthomyxovirus replication, what does viral polymerase use to prime viral mRNA synthesis
- The viral polymerase steals caps from nascent host mRNAs and uses them to prime viral mRNA synthesis