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Influenza Flashcards

1
Q

What is the influenza virus?

A
  • orthomyxoviridae family
  • segmented
  • ssRNA which means that the different viral proteins are encoded on different pieces of RNA, take key protein for vaccine, pandemic strains
  • enveloped virus- spread through aerosol droplets
  • helical nucleocapsid
  • 3 genera (subgroups)- A, B, C
  • most flu is A or B
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2
Q

Key viral proteins of flu?

A
  1. Hemagglutinin (HA)
  2. Neuraminidase (NA)
  3. M2
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3
Q

Functions of Hemagglutinin (HA)?

A
  1. attaches to sialic acid residues
    - binds different types of human HA vs Avian HA
    - avian strains dont affect humans usually, different affinity
  2. mediates viral cell fusion
    - requires cleavage of HA by cell proteases
    - requires low pH mediated conformational change in HA
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4
Q

Functions of Neuraminidase (NA)?

A
  • cleaves sialic acid residues (virus can be released to affect new cells)
  • promotes spread by aiding in release of virus from cells
  • cleaves sialic acid residues in mucus, prevents mucus from inhibiting binding
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5
Q

Functions of M2?

A
  • forms ion channel through envelope of virus, important in entry
  • allows H+ into viral core once the endosome is acidified
  • low pH promotes dissociation of the nucleocapsid protein and viral genome
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6
Q

Influenza A?

A
  1. 18 HA and 11 NA subtypes are identified
    - water fowl is reservoir for HA and NA subtypes
  2. 3 HA and 2 NA subtypes have been associated with human strains (seasonal flu)
    - H1N1 and H3N2- current seasonal flu
    - 2009 H1N1- pandemic strain (swine flu) has replaced prior seasonal H1N1 (vaccine covers H1N1 since 2009)
  3. influenza strains infecting birds and pigs are called avian or swine influenzas
    - HA and NA subtypes for avian and swine stains are antigenically distinct from same strains in humans
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7
Q

Avian influenza?

A
  1. naturally occurring among wild aquatic birds
    - can infect domestic poultry and other birds
    - usually does not infect humans
  2. categorized as low pathogenic (LPAI) or high pathogenic avian influenza (HPAI)
  3. HPAI (H5 and H7 subtypes)
    - mortality (for birds and poultry) can be 90-100%
    - control of outbreaks involves quarantines of exposed flocks with culling if disease is detected
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8
Q

Outbreaks of avian flu in people?

A
  1. H5N1- bird flu
    - 1997 outbreak in Hong Kong
    - re-emerged in 2003, more virulent now
    - currently circulating in Asia, Africa, Middle East
    - 52% fatality rate
  2. H7N9
    - first reported in 2013 in east China
    - more infectious, 40% fatality rate
  3. no sustained person to person transmission
    - most cases linked to exposure to contaminated poultry
    - limited person to person spread among families
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9
Q

Avian influenza in US?

A
  1. HPAI H5 viruses have been detected in US
    - in poultry flocks and wild birds
  2. reassortant H5N1 is genetically different from Asian origin of H5N1
  3. none HPAI H5 viruses seen in US have been associated with infections in people
    - do not contain markers for increased virulence or ability to spread among people
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10
Q

Swine influenza?

A
  1. influenza commonly circulating in swine
    - swine triple reassortant (tr) H1N1 (mix of human, avian, swine)
    - trH3N2v and trH1N2v circulating in US
    - subtypes causing sporadic infections in humans are called variant viruses
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11
Q

Outbreaks of swine flu in people?

A
  1. pandemic strain from 2009
    - called H1N1pdm09
    - sequencing indicated it was a swine strain of influenza, however it was not circulating in swine
    - emerged as human pandemic in 2009
    - now it is seasonal strain of flu
  2. flu A H3N2 variant virus (H3N2v)
    - detected in US pigs in 2010 and humans in July 2011
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12
Q

H3N2 variant virus?

A
  1. contains matrix (M) gene from the 2009 H1N1 pandemic virus
  2. spreads more easily from pigs to people than other variant viruses
    - main risk factor for infection is exposure to pigs
    - not easily transmitted person to person
  3. most cases to date have occurred in children
  4. mild with symptoms similar to seasonal flu
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13
Q

What does elastase do in the lung? steps of activation?

A
  1. it is a protease that cleaves hemagglutinin in the Golgi of more virulent strains which is the first step of activating the fusion glycoprotein
  2. acidification endosome by protons entering to mediate fusion
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14
Q

Why is acidification of the endosome important?

A
  • activates cleaved HA
  • passage of ions through M2 helps dissociate the nucleocapsid protein from viral RNA, which helps with uncoating
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15
Q

What happens after uncoating and release of viral RNA?

A
  1. viral proteins and more copies of viral genome are made
  2. envelope proteins (HA, NA, M2) are processed and sent to the cell surface
  3. NA cleaves surface sialic acid so that the new particle can be released
  4. M1 helps coordinated assembly, virus buds from plasma membrane
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16
Q

Why do annual epidemics and pandemic influenza occur each year?

A
  • antigenic variation of flu A
    1. antigenic drift (epidemics)
  • point mutations in HA and NA glycoproteins
  • population may have cross reactive antibodies providing partial immunity
  • responsible for mild or moderate epidemics
    2. antigenic shift (pandemics)
  • major antigenic change due to reassortant of HA and NA glycoproteins
  • population has little or no protective immunity
  • responsible for serious epidemics and pandemics
17
Q

Potential pandemic viruses?

A
  1. original hypothesis- pandemic strain will be the result of antigenic shift, occurring in pigs
    - both human and avian subtypes can replicate in pigs
    - may require adaptations in humans in order to replicate more efficiently in human cells
  2. HPAI H5- avian strain that can infect humans
    - little human to human transmission prevents it from becoming a pandemic strain at this point
  3. 2009 H1N1 - swine flu
18
Q

Models for generation of pandemic flu viruses? reassortant in pigs? (22)

A

-in classical genetic reassortant model, avian and human viruses bind their respective receptors in pig tracheal epithelium

19
Q

Models for generation of pandemic flu viruses? reassortment in humans? (23)

A

-an avian virus may infect a human and reassert with a human virus

20
Q

Models for generation of pandemic flu viruses? adaptation in pigs? (24)

A
  • in adaptation model, avian viruses acquire the ability to replicate efficiently in humans by adapting to human receptor in pigs
  • the change is mediated by a mutation in hemagglutinin gene
21
Q

Models for generation of pandemic flu viruses? adaptations in humans? (25)

A

-an avian virus may infect a human and acquire the ability to recognize the receptor on human epithelial cells, leading to efficient replication in humans and the ability to spread from human to human

22
Q

2009 H1N1?

A
  1. 2009 H1N1 contains H and N subtypes from swine strain of flu
    - a different virus than human H1N1
    - people did not have protective immunity
  2. reassortant virus
    - swine flu from Europe and Asia
    - swine flu in North America (genes of swine, human and avian origin)
  3. 2009 H1N1 is not present in pigs
  4. virus is easily transmitted person to person
23
Q

Avian influenza H5N1? where did it come from? (30)

A
  1. 1997, chickens began dying on farms in Hong Kong
    - virus responsible had subtype H5
  2. went quiet then reemerged in 2003 more virulent
24
Q

AI/H5 assessment from CDC?

A
  • in birds has become endemic in some areas, will continue to infect people
  • person to person is unusual and has not continued beyond one person
  • genetic reassortment between human strains and H5 has not been seen
  • some resistance to one class of flu antivirals and second class is still effective
25
Q

Avian flu H7N9?

A
  1. all genes from avian strains
    - HA similar to A (H7N3) in ducks in east china
    - NA gene similar to N9 virus in ducks in china and korea
    - 6 genes from A (H9N2) in poultry in Asia
  2. signs of adaptation to replication in mammals
    - bind to mammalian cell receptors
    - replicate at mammalian body temp
  3. causes severe pneumonia
  4. most cases involve exposure to poultry
    - live poultry markets
    - poultry do not show signs of infection, so it is hard to trace exposure
    - no sustained human to human transmission
  5. sensitive to NA inhibitors
  6. no commercially available vaccines
26
Q

Could avian strains of flu become pandemic strains?

A
  1. circulation in humans (or pigs) provides opportunity to adapt to replication in humans
  2. acquiring mutations in HA could allow virus to more readily bind to human cells
    - develop ability to spread person to person
  3. adaptation to mammalian cells may require changes in other viral proteins
    - mutations to viral polymerase to optimize interaction with host cell factors
  4. both H5N1 and H7N9 strains are being monitored for evidence of adaptation to replication in people
    - some evidence of adaptation in H7N9
  5. either virus could become a pandemic strain if it acquires the ability to easily transmit human to human
    - there appears to be more concern about H7N9 causing pandemic than H5N1

IP (29 decks)

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