Influenza viruses Flashcards
1
Q
Genomics of the influenza virus
A
- Many different types (A, B, C) but all are negative sense ssRNA
- They are enveloped derived from host cell membrane, w/ hemaglutinin (HA), neuraminidase (NA), and M protein
- HA: viral attachment protein, allows virus to fuse to cells (is the target of neutralizing Ab)
- NA: cleaves the bound sialic acid that keeps the virus from releasing (inhibited by tamiflu/relenza)
- M2: membrane protein that forms channel that allows for uncoating of viral genome by lowering the pH of the endosome (inhibited by amantadine)
- The transcriptases (PA, PB1/2) for influenza are error prone and causes mutations which lead to antigenic drift (H1->H2)
- Antigenic drift is why we get shots every year
2
Q
Viral replication cycle
A
- Binding (HA binds to sialic acid residues on receptors) followed by fusion of the virus w/ its endosome (via acidification of the endosome thru M2)
- Fusion is followed by uncoating and release of the nucleocapsid, which can now undergo transcription and replication
- Viral proteins synthesized and assembled into new virons, which bud off the cell
- Segmented genome of the virus (genome is broken up over many RNA strands) allows for reassortment of segments (Ag shift)
3
Q
Pandemics (antigenic shift)
A
- Only influenza A can cause a pandemic, since it’s a zoonosis disease
- When influenza A infects another animal species that already has an influenza A virus of a different strain, those two strains may share parts of their segmented genome (random association)
- If the genomes combine in a certain way the virus will have new HA (and other) genes that humans have not seen before
- This makes the virus much more virulent, can affect multiple continents
4
Q
Antigenic drift
A
- Mutations in the HA/NA proteins build up overtime and change the virulence of influenza viruses and can make them unrecognizable to the immune system
- Since these are gradual small changes they cause local outbreaks of both influenza A and B
5
Q
Pathogenesis of influenza infection
A
- Cytotoxic effect caused by viral replication causes epithelial tissue loss
- Mostly in URT but can affect the lungs
- Immunopathologic effect by host: epithelial damage, flu Sx
- Bacterial superinfection: viral infection exposes binding sites for bacteria and promotes their adhesion
- Complications of influenza: exacerbation of underlying pulm or cardio diseases, secondary bacterial PNA, primary influenza PNA, neuro syndromes (guillain-barre, encephalitis, Reye’s)
6
Q
Virulence factors
A
- Error-prone RNA polymerase facilitates major genetic changes, especially on HA and NA proteins (antigenic drift)
- Segmented genome and coinfection lead to genetic reassortment (antigenic shift)
7
Q
Influenza vaccines
A
- Seasonal vaccines predict which strains will be most virulent, and choose 3 to immunize people to
- Pregnant women see most severe complications, for both inactivated and attenuated vaccines
- 2009 H1N1 flu should be suspected if the pt has an acute febrile respiratory illness or sepsis-like syndrome
- Can be confirmed by PCR or viral culture
- Rx of the flu is tamiflu or relenza, both are NA inhibitors
