MI: Pandemic Flu Flashcards
Name four big flu pandemics that occurred in the last 200 years.
- Spanish flu (1918)
- Asian flu (1957)
- Hong Kong flu (1968)
- Swine flu (2009)
What is the natural reservoir for Influenza A?
Ducks
originates in animals crosses into humans –> pandemics
Why does influenza cause respiratory disease in humans?
The virus has a haemaggluttinin (HA) protein which must be cleaved for the virus to be able to fuse with the endosome membrane and release its genome into the host.
Human airway tryptase found in the lining of the lung is capable of cleaving HA.
NOTE: There are some mutated forms of influenza that do not require cleavage of HA to be able to enter host cells (these are particularly virulent)
What causes seasonal influenza
Influenza A - H1,H3
Influenza B
Describe the influenza life cycle.
- The virus attaches to cells via haemagluttin to the sialic acid receptor
- They enter through endosomes
- The acidity of the endosome triggers a fusion event by which the virus releases its genome into the host cell
- The genome travels to the nucleus and takes over host factors to drive transcription and translation
- New viral products are produced, which assemble at the surface of the cell and bud off producing hundreds of copies of the virus
Which specific mutation is associated with enabling influenza to cross into humans from birds?
P2 627K (polymerase protein)
replicate efficiently in human airway + transmit between people through air
Which current bird flu virus poses the biggest pandemic risk?
H7N9
NOTE: H5N1 is also very virulent
Other than a point mutation, how else can genes required for transmission into humans be acquired by viruses?
-
Reassortment - when single cells get infected by both a human and bird virus.
- Their RNA will shuffle producing a bird virus that has the capability of infecting humans.
- This is a quick way of viruses acquiring virulent traits - it is an example of antigenic shift
What trait must influenza viruses acquire in order to be able to successfully cause a pandemic in humans?
Surviving outside the host for longer - humans aren’t crammed together as much as birds/chickens etc.
What acts as a barrier to viral entry within the human respiratory tract?
Mucus - human viruses have evolved the ability to chop through mucus
What was an unusual feature of the 2009 swine flu pandemic in the UK?
The elderly were relatively spared possibly because they have been exposed to a similar virus in the past
Which features increase the risk of severe disease during the swine flu pandemic?
- Receiving a high infectious dose directly to the respiratory tract
- Acquired a mutant virus
- Acquired a bacterial superinfection
- Comorbidities
- Genetic predisposition (e.g. IFITM3 mutation)
What is the mechanism of action of amantidine?
Targets the M2 ion channel
What are the limitations of amantidine?
- A single amino acid mutation (S31N) renders the virus resistant
- Does not work against influenza B, pH1N1 and seasonal H3N2
List three examples of neuraminidase inhibitors.
- Oseltamavir (tamiflu) - oral
- Zanamivir (relenza) - inhaled or IV
- Peramivir - IV
List two examples of polymerase inhibitors.
- Favipiravir
- Baloxavir
What is the role of antivirals in pandemics?
- Used in the first 3-6 months of a pandemic
How long does it take to manufacture an influenza vaccine?
3-6 months
What type of vaccine is the seasonal influenza vaccine used in high risk groups?
Purified fraction containing HA and NA of an inactivated virus
NOTE: often needs to be given with an adjuvant
What type of flu vaccine is given to school-aged children?
Live-attenuated vaccine
NOTE: this is a cold-adapted virus that is sprayed into the child’s nose. This provides broader and more cross-reactive immunity.
By making reference to the structure of haemagglutinin, how could a universal flu vaccine be produced?
- Most antibodies bind to the head of the HA molecule which is very plastic and changes every year
- There is another antibody binding site on the stalk of the HA molecule, which appears to be invariant
- The generation of antibodies against this invarant patch may allow antibodies to cross-react with every type of influenza
What do influenza pandemic viruses eventually end up becoming?
They eventually become seasonal influenza viruses
Role of neuraminidase inhibtitor
Give example
Prevents virous which have been replicated being able to leave the infected cell
Neuraminidase normally cleaves the sialic acid from cell
Tamiflu, oseltamivir
what type of vaccine is given for seasonal flu
children - live attenuated, intranasal, can only replicate in nasal cells - cold adapted
over 65 - inactive, Haemagluttinin unit
