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
2
Q
Key viral proteins of flu?
A
- Hemagglutinin (HA)
- Neuraminidase (NA)
- M2
3
Q
Functions of Hemagglutinin (HA)?
A
- attaches to sialic acid residues
- binds different types of human HA vs Avian HA
- avian strains dont affect humans usually, different affinity - mediates viral cell fusion
- requires cleavage of HA by cell proteases
- requires low pH mediated conformational change in HA
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
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
6
Q
Influenza A?
A
- 18 HA and 11 NA subtypes are identified
- water fowl is reservoir for HA and NA subtypes - 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) - 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
7
Q
Avian influenza?
A
- naturally occurring among wild aquatic birds
- can infect domestic poultry and other birds
- usually does not infect humans - categorized as low pathogenic (LPAI) or high pathogenic avian influenza (HPAI)
- 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
8
Q
Outbreaks of avian flu in people?
A
- 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 - H7N9
- first reported in 2013 in east China
- more infectious, 40% fatality rate - no sustained person to person transmission
- most cases linked to exposure to contaminated poultry
- limited person to person spread among families
9
Q
Avian influenza in US?
A
- HPAI H5 viruses have been detected in US
- in poultry flocks and wild birds - reassortant H5N1 is genetically different from Asian origin of H5N1
- 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
10
Q
Swine influenza?
A
- 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
11
Q
Outbreaks of swine flu in people?
A
- 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 - flu A H3N2 variant virus (H3N2v)
- detected in US pigs in 2010 and humans in July 2011
12
Q
H3N2 variant virus?
A
- contains matrix (M) gene from the 2009 H1N1 pandemic virus
- 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 - most cases to date have occurred in children
- mild with symptoms similar to seasonal flu
13
Q
What does elastase do in the lung? steps of activation?
A
- it is a protease that cleaves hemagglutinin in the Golgi of more virulent strains which is the first step of activating the fusion glycoprotein
- acidification endosome by protons entering to mediate fusion
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
15
Q
What happens after uncoating and release of viral RNA?
A
- viral proteins and more copies of viral genome are made
- envelope proteins (HA, NA, M2) are processed and sent to the cell surface
- NA cleaves surface sialic acid so that the new particle can be released
- M1 helps coordinated assembly, virus buds from plasma membrane
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
- 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 - HPAI H5- avian strain that can infect humans
- little human to human transmission prevents it from becoming a pandemic strain at this point - 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
- 2009 H1N1 contains H and N subtypes from swine strain of flu
- a different virus than human H1N1
- people did not have protective immunity - reassortant virus
- swine flu from Europe and Asia
- swine flu in North America (genes of swine, human and avian origin) - 2009 H1N1 is not present in pigs
- virus is easily transmitted person to person
23
Q
Avian influenza H5N1? where did it come from? (30)
A
- 1997, chickens began dying on farms in Hong Kong
- virus responsible had subtype H5 - 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
- 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 - signs of adaptation to replication in mammals
- bind to mammalian cell receptors
- replicate at mammalian body temp - causes severe pneumonia
- 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 - sensitive to NA inhibitors
- no commercially available vaccines
26
Q
Could avian strains of flu become pandemic strains?
A
- circulation in humans (or pigs) provides opportunity to adapt to replication in humans
- acquiring mutations in HA could allow virus to more readily bind to human cells
- develop ability to spread person to person - adaptation to mammalian cells may require changes in other viral proteins
- mutations to viral polymerase to optimize interaction with host cell factors - both H5N1 and H7N9 strains are being monitored for evidence of adaptation to replication in people
- some evidence of adaptation in H7N9 - 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
