Microbiology 19 - Influenza and Covid-19 Flashcards

1
Q

What drives zoonosis of influenza viruses from wild water fowl?

A

Antigenic drift

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2
Q

What must a mutation change to produce a pandemic-producing virus ?

A

Transmissibility between humans
Antigenic novelty

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3
Q

What is the mechanism of action of amantidine, and what is it used for?

A

Targets M2 ion channel
Used to treat strains types of influenza virus

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4
Q

3 drug classes against influenza

A
  1. Amantidine
  2. Neuraminidase inhibitor
  3. Polymerase inhibitor
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5
Q

What class of drug is oseltamivir?

A

Neuraminidase inhibitor

Neuraminidase is the enzyme (spike protein) that cleaves sialic acid to allow virus to exit the cell and infect other cells

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6
Q

What influenza vaccines are used in the UK?

A
  1. Inactivated vaccine
    - Haemaglutinnin and neuraminidase proteins
    - used in adults
  2. Live attenuated (used as a nasal spray)
    - used in children ONLY

not effective in adults because they’ve encountered the viral flu antigen before

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7
Q

What is the most important reason why SARS 2003 was so much easier to contain than SARS Covid 19?

A

Patients had easily-identifiable symptoms that developed quickly and so could be isolated - covid-19 is much more insidious!

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8
Q

Most likely origin of COVID-19

What is a likely secondary host?

A

Horseshoe bats

Likely secondary host: pangolins

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9
Q

Describe the genome of SARS-Cov2

A

Huge single-stranded RNA genome

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10
Q

How does covid bind to cells to gain entry?

A

They use their spike protein to bind to ACE2 receptor in the host

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11
Q

How long after infection is covid infectious?

A

3 days

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12
Q

From which day is COVID-19 symptomatic?

A

Day 5

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13
Q

What is the time course of covid-19 infection?

A
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14
Q

What is the predominant variant of COVID?

A

Omicron - current vaccine is less effective against it, but also causes less severe infection

Omicron has a large number of Spike mutations that affect antibody neutralization

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15
Q

Recall 2 important factors that will be at elevated serum levels in covid infection, and can be useful clinically?

A

IL-6
D-dimer

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16
Q

What benefit is remdesivir shown to have in coronavirus?

A

Shortens time to recovery

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17
Q

In which patients is dexamethosone effective at reducing coronavirus death?

A

In those who are receiving oxygen

*dexatheasone is used in ITU setting

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18
Q

Monocloncal antibodies and small molecule inhibitors for covid

A

Monoclonal: Regeneron, Sotrovimab

Small molecules:

1) Molnupiravir: targets polymerase, nucleoside analgue
2) Paxlovid: targets protease

19
Q

Natural reservoir of influenza A virus

A
  • wild birds like ducks, geese and **migratory waterfowl (mostly)**
  • From this reservoir, the virus can cross over to other animals
  • It can also end up in mammals including humans
20
Q

How does influenza enter the human cell and spread?

A
  • The virus is particularly vulnerable during the transmission phase when it is going in between people
  • They attach to cells via sialic acid receptors
  • They enter through endosomes
  • The acidity of the endosome triggers a fusion event by which it releases its genome into the cell
  • The genome then travels to the nucleus and takes over host factors to drive transcription and translation
  • New viral products are produced (proteins and genome)
  • They will assemble at the surface of the cell and bud off to produce hundreds of copies of the virus
21
Q

2 possible outcomes when avian influenza A crosses over into humans:

A

1) Sometimes they can just cause a zoonoses which is a dead end:
- can cause a severe disease but does not transmit on to other human
- People exposed to the animal can get the virus
- but not as much of a Public Health issue, as it will not cause a large outbreak
2) However, if the virus undergoes various MUTATIONS it can transform from avian to human virus:
- leading to pandemic influenza
- Pandemic influenza transforms into seasonal influenza

→ undergoes antigenic drift and human adaptation

→ changing a little bit year on year (hence vaccine is updated each year)

-Therefore, all current human influenza was originally a pandemic flu

which was originally a bird virus

-It has undergone mutations to go from a virus in birds to now infecting humans

22
Q

Why does influenza B, C and D not cause pandemics?

A

Not in animal reservoirs

Do not exist in antigenically different form to human variants

→ humans can recognise and act against them

23
Q
A
24
Q

Can you use influenza drugs in combination?

A

No- but this is worrying as this risks viruses developing mutations against one antiviral

25
Q
A
26
Q
A
27
Q

What famiy is influenza virus from?

A

Orthomyxoviridiae

28
Q

Structure of influenza virus?

A
  • enveloped virus
  • filamentous morphology
  • negative sense segmented RNA genome (8 segments)
29
Q

3 key properties of a pandemic virus

A
  1. novel antigenicity
  2. can replicate well in the human airway
  3. can spread rapidly between people
30
Q

what are the different antigenic flues that affect humans each year?

A
  1. Influenza A H1: peaks beginning of January
  2. Influenza A (H1N1)- peaks end of December

3. Influenza B (peaks March)

31
Q

What does the influenza vaccine given to high risk groups contain?

What about the one given to children?

A

Purified fraction with HA and NA of inactivated virus

Children: live attenuated vaccine

32
Q

What is the natural reservoir of influenza virus?

A

Ducks

33
Q

Why is human-human transmission of bird flu difficult?

A

Bird flue - H5N1

difficult as the virus can’t replicate in the cold temperatures of the upper airway

34
Q

What are the two main receptors on influenza and what are they used for?

A

Haemaggglutinin: binds sialic acid receptors to allow entry of the virus. Virus envelope fuses with the endosome–>release of virus

Neuraminidase: i.e. sialidase, cleaves residues allowing exit of virions from host cell; disrupts mucin barrier

35
Q

What does H5N1 actually mean?

A

h= haemagglutinin

n= neuraminidase

36
Q

What is antigenic drift?

A

Accumulation of point mutations changes the nature of the antigen over time

eg thsi is what happens between the different strains of influenza

37
Q

What is antigenic shift?

A

Recombination of genomic segments during assembly and egress of two co-infecting flu strains –> rapid potentially whole antigenic change for a viral strain

–>potentially allows for exchange of RNA segments between human and animal strains

38
Q
A
39
Q

What are the two steps required for an animal virus–> human pandemic

A
  1. acquire the abilty to INFECT human cells either by:
    a) acquire mutation in pOLYMERASE protein or
    b) recombination of gene segments (when another virus that’s capable of infecting human cells also infects at the same time)

and:

  1. Acquire the ability to transmit between humans
40
Q

What was unusula about the swine flu pandemic?

A

elderly people were relatively spared

41
Q

How does amantadine work? why is there resistance?

A

targets m2 ion channel

single amino acid mutation in M2 (S31N) makes virus resistant

*NB: only works for influenza A (not influenza B)

42
Q

Give an example of a neuraminidase inhibitor. what is its MOA ?

A

Oseltamivir - tamiflu

Zanamivir- relenza

**need to use them <48 hours after infection for them to be effective

Neuraminidase inhibitors- prevent viruses from spreading through the respiratory tract (i.e. target spread rather than entry)

43
Q
A
44
Q

What type of vaccine is SARS COV2 vaccine?

A

mRNA vaccines encoding stabilized spike