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ZAHRAH MICRO > MI: Pandemic and Covid > Flashcards

MI: Pandemic and Covid Flashcards

1
Q

What three ingredients needed for pandemic?

A
  1. Novel antigenicity
  2. Efficient replication in human cells
  3. Efficient transmission between people
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2
Q

Pathogens with pandemic potential?

A
  1. SARS-Cov-2
  2. Influenza
  3. Dengue
  4. Zika
  5. West Nile Virus
  6. Nipath
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3
Q

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

A
  1. Spanish flu (1918) - H1N1 influenza A
  2. Asian flu (1957) - H2N2 influenza A
  3. Hong Kong flu (1968) - H3N2 influenza A
  4. Swine flu (2009) - H1N1 influenza A
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4
Q

What is the natural reservoir of influenza A viruses?

A

aquatic birds

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5
Q

Name the important components of an influenza virus

A

Haemagluttinin
Neuraminidase
RNA (8 segments)

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6
Q

Why does influenza cause respiratory disease in humans?

A

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)

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7
Q

Why don’t all avian influenza viruses cause disease?

A

There is incompatibility with the human host allowing for enough time for immune system to clear the virus

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8
Q

What protein do birds have that humans don’t that influenza viruses can co-opt?

A

ANP32

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9
Q

What host protein do humans have that inhibit influenza polymerase activity?

A

Butyrophilin A3 (restriction factor)

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10
Q

What mutation in the influenza polymerase gene improve compatibility with human host?

A

PB2 E627E to PB2 E627K

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11
Q

Describe the influenza life cycle.

A
  • 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
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12
Q

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

A

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

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13
Q

Antigenic shift v antigenic drift?

A

Antigenic shift - abrupt and drastic changes in viral antigens (not sufficient to bring about a pandemic)
Antigenic drift - small and gradual changes in viral antigens

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14
Q

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

A

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

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15
Q

Difference between sialic acid linkage in humans and birds?

A

In humans it is linked to alpha2-6 but birds is almost entirely alpha 2-3

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16
Q

How can a virus adapt for transmission in humans via the sialic acid receptor?

A

It acquires an affinity for human receptors and changes its haemagluttinin receptor shape

17
Q

How might airborne droplet transmission destroy a virus?

A

The concentration of respiratory secretion components will decrease - virus destroyed unless stable

18
Q

how do neuraminidase inhibitors work?

A

neuraminidase cannot cleave the receptor so virus reinfects same cell (which is dying) preventing further viral replication

19
Q

List three examples of neuraminidase inhibitors

A

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

20
Q

List two examples of polymerase inhibitors.

A

Favipiravir
Baloxavir

21
Q

What is the role of antivirals in pandemics?

A

Used in the first 3-6 months of a pandemic

22
Q

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

A

Purified fraction containing HA head of an inactivated virus

NOTE: often needs to be given with an adjuvant

23
Q

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

A

Live-attenuated vaccine

This is a cold-adapted virus that is sprayed into the child’s nose. This provides broader and more cross-reactive immunity.

24
Q

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

A

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 invariant patch may allow antibodies to cross-react with every type of influenza (broadly-neutralising antibodies)

25
Q

What is the mechanism of action of amantidine?

A

Targets the influenza A M2 ion channel. This impairs viral replication

26
Q

What are the limitations of amantidine?

A

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

27
Q

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

A

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

28
Q

Why did we contain SARS?

A

Because most people who got it were quite symptomatic and so less transmission

29
Q

How does SARS CoV2 enter the cells?

A

ACE2

30
Q

What are the natural reservoirs of SARS- CoV2?

A

Bats and Pangolins

31
Q

what is the time course of SARS CoV2

A

Day 3 = positive and infectious
Day 5 = symptomatic
Day 8 onwards = virus positive and not infectious
OR
Day 7 - 10 = virus dissemination and immunopathology (cytokine storm in the lungs)

32
Q

What is a cheap and effective medication used to treat patients hospitalised in ITU because of SARS- CoV2?

A

Dexamethasone

33
Q

what vaccine was implemented during the pandemic?

A

mRNA vaccines (nucleoside-modified)
uses ‘locks’ to keep virus in prefusion spike

34
Q

What mutations are occurring in different strains of COVID?

A

spike mutations

ZAHRAH MICRO (24 decks)

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