MI: Pandemic Flu

Question 1

Name four big flu pandemics that occurred in the last 200 years.

Answer 1

• Spanish flu (1918)
• Asian flu (1957)
• Hong Kong flu (1968)
• Swine flu (2009)

Question 2

What is the natural reservoir for Influenza A?

Answer 2

Ducks

Question 3

Why does influenza cause respiratory disease in humans?

Answer 3

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)

Question 4

Describe the influenza life cycle.

Answer 4

• The virus attaches to cells via 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

Question 5

Which specific mutation is associated with enabling influenza to cross into humans from birds?

Answer 5

B2 627K (polymerase protein)

Question 6

Which current bird flu virus poses the biggest pandemic risk?

Answer 6

H7N9

NOTE: H5N1 is also very virulent

Question 7

Other than a point mutation, how else can genes required for transmission into humans be acquired by viruses?

Answer 7

• 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

Question 8

What trait must influenza viruses acquire in order to be able to successfully cause a pandemic in humans?

Answer 8

Surviving outside the host for longer - humans aren’t crammed together as much as birds/chickens etc.

Question 9

What acts as a barrier to viral entry within the human respiratory tract?

Answer 9

Mucus - human viruses have evolved the ability to chop through mucus

Question 10

What was an unusual feature of the 2009 swine flu pandemic in the UK?

Answer 10

The elderly were relatively spared possibly because they have been exposed to a similar virus in the past

Question 11

Which features increase the risk of severe disease during the swine flu pandemic?

Answer 11

• 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)

Question 12

What is the mechanism of action of amantidine?

Answer 12

Targets the M2 ion channel

Question 13

What are the limitations of amantidine?

Answer 13

• A single amino acid mutation (S31N) renders the virus resistant
• Does not work against influenza B, pH1N1 and seasonal H3N2

Question 14

List three examples of neuraminidase inhibitors.

Answer 14

• Oseltamavir (tamiflu) - oral
• Zanamivir (relenza) - inhaled or IV
• Peramivir - IV

Question 15

List two examples of polymerase inhibitors.

Answer 15

• Favipiravir
• Baloxavir

Question 16

What is the role of antivirals in pandemics?

Answer 16

• Used in the first 3-6 months of a pandemic

Question 17

How long does it take to manufacture an influenza vaccine?

Answer 17

3-6 months

Question 18

What type of vaccine is the seasonal influenza vaccine used in high risk groups?

Answer 18

Purified fraction containing HA and NA of an inactivated virus

NOTE: often needs to be given with an adjuvant

Question 19

What type of flu vaccine is given to school-aged children?

Answer 19

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.

Question 20

By making reference to the structure of haemagglutinin, how could a universal flu vaccine be produced?

Answer 20

• 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

Question 21

What do influenza pandemic viruses eventually end up becoming?

Answer 21

They eventually become seasonal influenza viruses