Micro 5 - pandemic flu Flashcards
natural reservoir for influenza A virus
Ducks
Why does influenza virus only cause respiratory disease?
influenza requires cleavage of HA by host cell try-tases, notably human airway tryptase (HAT) which is only found in the lung!
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which strains of influenza do we worry about and why?
H5N1 and H7N9. They have a mutation of the cleavage site of HA so they can disseminate to the whole body and not just the lungs.
what can infection with H5N1 lead to in humans?
Hypercytokinaemia –> ARDS
How does influenza virus enter cells
Binds to sialic acid receptors on human cells with its haemagglutinin
What needs to happen to influenza virus to affect human cells?
Once the haemagluttinin has bound to sialic acid receptors in host URT cells, it requires cleavage by host cell proteases - HUMAN AIRWAY TRYPTASE - to allow entry
name one type of influenza virus which does not require HAT cleavage of HA to gain cell entry
H5N8
• There is a specific mutation(single amino acid change in polymerase) that is associated with bird flu being able to cross into human - what is it?
PB2 mutations
what is reassortment?
when one human cell is infected by both an avian virus and a human virus, they then shuffle their RNA –> bird virus with ability to infect humans
what is reassortment an example of?
antigenic shift
what 2 things are required for an animal virus to become a human pandemic?
1) ability to infect human cells (either by PB2 mutation or reassortment)
2) Human to human transmission
how are human influenza viruses transmitted?
respiratory droplets
2 main barriers to influenza viral entry
mucous
Avian HAwould need to mutate to be able to recognise human sialic acid receptors
which variant of influenza caused the 2009 swine flu pandemic?
H1N1
how does an influenza virus compete with human mucus barrier to infect the respiratory tract?
Neuraminidase cuts through sialic acid in mucous
Which age ranges did H1N1 tend to affect and why?
Younger people as older people tend to have seen the virus before
specific genetic predisposition to severe H1N1 infection?
IFITM3 mutation
Amantadine - MOA?
Why is it useless?
targets the M2 ion channel
single point mutation in M2 renders the virus resistant
Name 2 neuraminidase inhibitors?
Oseltamivir (tamiflu)
Zanamivir (relenza) - dry powder
what does the influenza vaccine tend to target and what do influenza anti-virals target
Vaccine –> HA
Anti virals –> NA
EXAMPLE OF polymerase inhibitors (not currently used in UK)
Favipravir, baloxavir
Describe the composition of the influenza vaccine given to high risk groups in the UK?
Purified fractions of HA and NA from inactivated viruses
Diff btw influenza vaccine given to children vs elderly
elderly: inactivated cvaccine
children: live attenuated (intranasal)
what do influenza pandemic viruses evolve into?
seasonal influenza viruses