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107 Cards in this Set
- Front
- Back
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What family does influenza belong to?
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Orthomyxoviridae
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What viruses are part of this family?
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Influenza A/B/C
Isavirus Thogotovirus |
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What does influenza A infect?
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Humans, pigs, birds, horses
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What does influenza B infect?
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Humans, seals
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What does influenza C infect?
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Humans, pigs
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Which of these viruses have caused all human pandemics?
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Influenza A
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Which cause the annual human epidemics?
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Influenzas A and B
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What is the reservoir for influenza A?
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Wild waterfowl
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Describe influenza A
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Pleomorphic morphology
Enveloped particles 8 segments (-)ssRNA |
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What are the neutralization antigens of influenza A?
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HA and NA
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What part of influenza does the host IR respond to?
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HA and NA
Form neutralizing Ab vs this |
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What does pleomorphic morphology entail?
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Spheres or filament form
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How many segments do flus B and C have?
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B: 8 segments
C: 7 segments |
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What are all vaccines vs flu based on?
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HA and NA that is on the surfacve of the circulating virus
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Describe the influenza structure
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Envelope: gotten from host cell through budding
3 ptns: HA, NA, MZ |
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What part of influenza does the host IR respond to?
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HA and NA
Form neutralizing Ab vs this |
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What does pleomorphic morphology entail?
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Spheres or filament form
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How many segments do flus B and C have?
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B: 8 segments
C: 7 segments |
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What are all vaccines vs flu based on?
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HA and NA that is on the surfacve of the circulating virus
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Describe the influenza structure
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Envelope: gotten from host cell through budding
3 ptns: HA, NA, MZ |
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What is the MZ ptn for?
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Forms ion channel
-->Important in entry |
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How many HA subtypes are there?
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16
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How many HA subtypes are there?
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9
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Where can all these subtype be found?
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In water fowl
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What are the confirmed subtypes in humans?
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H1N1, H1N2
H2N2 H3N2 H5N1 H9N2 H7N2, H7N3, H7N7 H10N7 |
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How are flus classified?
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Flu A-B-C/ Where it is isolated/ month/year of isolation (subtype)
Ex: A/Moscow/10/99(H3N2) |
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What was the dominant influenza strain in the early 1900s?
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H1N1
-->reappeared in the 1970s |
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What are the current dominant strains?
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H1N1
H3N2 |
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What is Ag drift?
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High mutation rate of RNA pol causes changes
-->Can make virus very pathogenic |
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What is Ag shift?
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Emergence of a new virus strain: interspecies transmission and/or reassortment of genomic RNA fragments (bird-->human, pig to human etc)
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What happens if one host is infected with 2 flu genomes?
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Their RNA genomes can get mixed up and new viruses carry mix of the virus
-->Get new viral strains |
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What is the hypothetic transmission route for interspecies transmission?
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Wild water fowl --> domestic water fowl --> quail/pig --> chicken --> human
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Which animal is very important to interspecies transmission? Why?
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Pigs
-->Pigs are teh mixing vessel, express both human and avian type influenza virus receptors on epithelial cells in trachea |
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How many ppl are affected by the seasonal flu?
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1 billion infections
3-5 million severe diseases 300-500 000 mortality annually |
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Which subtype was involved in the spanish flu?
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H1N1
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Which subtype was involved in the Asian flu?
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H2N2
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Which subtype was involved in the Hong Kong flu?
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H3N2
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What happened in the spanish flu?
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Over 50 million killed
First wave in the spring of 1918, second in the fall, third in 1919 2.5% mortality rate (usually only 0.1%) H1N1, avian like |
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What did ppl die of after they got the spanish flu?
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Bacterial and viral pneumonia
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What did this H1N1 cause immnunologically?
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Aberrant innate IR
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Which influenza ptns contribute to virulence?
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HA
PB2 |
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What happened in the Asian influenza?
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Outbreak 1957
Human/avian reassortant with avian virus H2 and N2 |
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Describe the Hong Kong influenza
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1968 outbreak
Human/avian reassortant with avian H3 |
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Describe Russian influenza
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1977outbreak
Re-emerging H1N1 Co-circulating with H3N2 in human population |
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Describe swine flu
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2009 outbreak
Reassortment btw human H3N2, H1N2 swine virus and Eurasian avian-like swine virus |
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Describe how new virus emerge
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Viruses combine with other flu viruses out there
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Describe the origin of the new H1N1
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Classical swine, North Ameerican avian and Human H3N2 combined in another pig
This new virus compbined with the eurasian avian-like swine in another pig Get new H1N1 (influenza A) >Recomb of 4 viruses |
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What makes influenza low pathogenic risk?
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Glu, Asp, Asn, single basic aa or RSEV deletion at C-terminus
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What makes the virus highly pathogenic?
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Lys, Asn, Ser, multiple basic ass, ESEV not deleted
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Why are multiple basic aa more potent than a single basic aa?
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Can be cleaved systemiically
.: deadly Happens in avian flu |
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Describe the life cycle of influenza virus
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Entry: Bind receptor on cell surface (SA)
Translocation into nucleus RNA T Ptn Tl (in cytoplasm) Virus assembly |
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Describe entry
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Endocytosis
-Go to late endosome, low pH, fusion of env with virus Then the viral genome is released into the cytoplasm |
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What needs to happen to HA to get into the cell?
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HA has to be cleaved into 2 domains: HA1/2
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What happens after SA is bound by HA?
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SA holds particles so that they can't leave the surface
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What does NA do?
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NA cleaves HA when viral particles are ready to go
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Entry
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Entry
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What are the 2 types of Sialic acid?
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SA-a2,3-Gal
SA-a2,6-Gal |
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Where is SA-a2,3-Gal found?
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In the GIT of AVIAN species
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Where is SA-a2,6-Gal found?
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In the tracheal epithelial tissues of HUMANs
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What receptor for SA do pigs express?
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Both of these
SA-a2,3-Gal SA-a2,6-Gal |
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What does this mean that the pig has both receptors?
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Both avian and human influenza can infect pig trachea tissue
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What is the receptor specificity determined by?
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The aa residues of the HA receptor binding pocket
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Describe HA maturation
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HA made as HA0 transcript
This needs to be cleaves into HA1 and 2 domains -->these 2 domains are linked by a S-S bond |
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What kind of a folding does HA1/2 have?
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B-shaped
Very critical structure |
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During thecleavage of the HA1/2 linkage, what happens if the HA has a single aa (Arg)?
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Low pathogenic avian viruses and non-avian influenza viruses
ONLY cleave by proteases in the respiratory and/or intestinal organs |
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Which flu virus is the exception to this?
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H7N7 equine flu
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What happens if the cleavage of the HA1/2 linkage results in multiple basic aa?
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Highly pathogenic
H5 or H7 viruses Cleaved by UBIQUITOUS proteases (furin, PC6) Leads to systemic infections |
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Are these more pathogenic strains a problem for humans
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Not right now
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Describe the domain structure of viral envelope ptn HA, of influenza
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HA1------ (Fusion peptide-HRA--HRB----TM)[HA2]
HA1/2 linked by S-S bond |
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What does influenza HA look like?
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Parainfluenza virus 5 fusion ptn (PIV5 F ptn)
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What do both of these envelope ptns have?
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Helix bundles
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Describe class I mb fusion ptns
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Globular head + helix bundle
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Describe Class II mb fusion ptns
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Found in Alphavirus and Flavivirus
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Do class II viruses have a helical structure?
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No
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What dtructure do class II mbs (Alpha/flavivirus) have post fusion?
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B-sheath folding
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Why is this type of folding used (B-sheath folding)?
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Helps fusion peptide anchor into the envelope
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What is the fct of these different structures?
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All serve th esame fct:
Support the binding site abd responsible for inserting the fusion peptide into cell mb and pulling the cell mb closer to viral mb -->get mb fusion |
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What is the trigger for fusion for Influenza viruses?
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Low pH
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Is low pH requierd for HIV mb fusion?
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No, that is a pH independent case
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Describe the VSV G ptn
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A third class of mb fusion ptns
Has a B helical strucutre in the head, but none in the stem Assumes a similar structure after fusion |
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Viral RNA transcription
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Viral RNA T
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Describe the structure of viral RNPs
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Packed very tightly
2+ ends of viral RNA captured by viral RNA Pol complex (formed by PA,PB1/2) |
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How does viral RNA T work in influenza?
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3 events
1)Pb2 binds the cap of cellular cap pre-mRNA 2) After binding, PA subunit cuts cellular mRNA 3) PB1 uses the cell mRNA as a primer to initiate viral RNA T |
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Virus assembly
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Virus assembly
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How many ptns does Influenza A have?
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11 ptn
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How many ptns does influenza C have?
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9 ptn
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Which 4 influenza ptns are required for viral assembly?
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HA
NA M1 M2 |
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How do these ptns work?
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HA and NA bind to the lipid raft domain (microdomain) on the plasma mb
M1 and M2 are then recruited to complete assembly and budding |
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Which ptns are the driving force of assembly?
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HA and NA
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How many particles are in each virion?
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8 (8 RNA segments in the virus particles)
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Describe Viral RNA packaging
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viral RNA come together (8/gp)
Go to the site of budding with HA, NA, M1, M2 Will then form long filamentous form |
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What was ddiscovered about the interaction of influenza with host factors?
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Found that for each step, there are many cellular factors, hijacked by virus
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What are the fcts of NS1 ptn?
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Limit IFN induction
Limit antiviral state Block cellular mRNA T Limit apoptosis Enhance its own viral mRNA Tl |
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How does NS1 limit IFN induction?
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Blocks RIG-I and OAS paths
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How is apoptosis limited?
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Through viral ptns
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What happens to influenza if it doesn't have NS1?
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Virus is very vulnerable
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What are the targets of influenza by antivirals?
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2 of them target Na
1 targets M2 |
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What does the one that targets M2 do?
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Goes into channel and blocks its fct
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What are the 2 antivirals that target NA?
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Zanamivir
Aseltamivir |
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What drug is used vs M2?
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Amantadine
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What are the different vaccines vs the flu?
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Seasonal flu vaccines
Seed virus Inactivated vaccines Live attenuated vaccines |
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Describe the seasonal flu vaccine
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H1N1 and H3N2 subtypes of human influenza A and an influenza B virus
Revised every 1-3 years tp included mutated HA and NA -->Form Abs vs them -->Trivalent vaccine |
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What is a seed virus?
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Make virus that is used in labs
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How is a seed virus made?
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By reassortment
contains HA and NA segments of circulating virus and segments of the H1N1 ->Includes HA's from H1N1, H3N2 and influenza B |
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How are inactivated vaccines made?
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In embryonated chicken eggs
Inactivated with formalin or B-propiolactone |
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What kind of a response do live attenuated vaccines elicit?
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Stronger humoral and cellular immune response
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What are tthe new approaches to making vaccines?
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Universal vaccine targeting the highly conserved ectodomain of M2 ptn
Virus like particles (M1,M2,HA,NA) Vectors: replication-incompetent adenovirus |
