Microbiology 19 - Influenza and Covid-19

Question 1

What drives zoonosis of influenza viruses from wild water fowl?

Answer 1

Antigenic drift

Question 2

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

Answer 2

Transmissibility between humans
Antigenic novelty

Question 3

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

Answer 3

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

Question 4

3 drug classes against influenza

Answer 4

1. Amantidine
2. Neuraminidase inhibitor
3. Polymerase inhibitor

Question 5

What class of drug is oseltamivir?

Answer 5

Neuraminidase inhibitor

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

Question 6

What influenza vaccines are used in the UK?

Answer 6

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

Question 7

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

Answer 7

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

Question 8

Most likely origin of COVID-19

What is a likely secondary host?

Answer 8

Horseshoe bats

Likely secondary host: pangolins

Question 9

Describe the genome of SARS-Cov2

Answer 9

Huge single-stranded RNA genome

Question 10

How does covid bind to cells to gain entry?

Answer 10

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

Question 11

How long after infection is covid infectious?

Answer 11

3 days

Question 12

From which day is COVID-19 symptomatic?

Answer 12

Day 5

Question 13

What is the time course of covid-19 infection?

Answer 13

Question 14

What is the predominant variant of COVID?

Answer 14

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

Question 15

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

Answer 15

IL-6
D-dimer

Question 16

What benefit is remdesivir shown to have in coronavirus?

Answer 16

Shortens time to recovery

Question 17

In which patients is dexamethosone effective at reducing coronavirus death?

Answer 17

In those who are receiving oxygen

*dexatheasone is used in ITU setting

Question 18

Monocloncal antibodies and small molecule inhibitors for covid

Answer 18

Monoclonal: Regeneron, Sotrovimab

Small molecules:

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

Question 19

Natural reservoir of influenza A virus

Answer 19

• 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

Question 20

How does influenza enter the human cell and spread?

Answer 20

• 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

Question 21

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

Answer 21

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

Question 22

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

Answer 22

Not in animal reservoirs

Do not exist in antigenically different form to human variants

→ humans can recognise and act against them

Question 24

Can you use influenza drugs in combination?

Answer 24

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

Question 27

What famiy is influenza virus from?

Answer 27

Orthomyxoviridiae

Question 28

Structure of influenza virus?

Answer 28

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

Question 29

3 key properties of a pandemic virus

Answer 29

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

Question 30

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

Answer 30

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

3. Influenza B (peaks March)

Question 31

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

What about the one given to children?

Answer 31

Purified fraction with HA and NA of inactivated virus

Children: live attenuated vaccine

Question 32

What is the natural reservoir of influenza virus?

Answer 32

Ducks

Question 33

Why is human-human transmission of bird flu difficult?

Answer 33

Bird flue - H5N1

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

Question 34

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

Answer 34

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

Question 35

What does H5N1 actually mean?

Answer 35

h= haemagglutinin

n= neuraminidase

Question 36

What is antigenic drift?

Answer 36

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

eg thsi is what happens between the different strains of influenza

Question 37

What is antigenic shift?

Answer 37

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

Question 39

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

Answer 39

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:

2. Acquire the ability to transmit between humans

Question 40

What was unusula about the swine flu pandemic?

Answer 40

elderly people were relatively spared

Question 41

How does amantadine work? why is there resistance?

Answer 41

targets m2 ion channel

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

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

Question 42

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

Answer 42

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)

Question 44

What type of vaccine is SARS COV2 vaccine?

Answer 44

mRNA vaccines encoding stabilized spike