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

Recall the process of influenza A cleavage

Answer 3

1. Viral spike proteins (most important is haemaglutinnin - HA)
2. Protease required to cleave HA is only found in airway (Human Airway Tryptase)
3. HAT cleaves influenza A at a specific site

Question 4

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

Answer 4

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

Question 5

3 drug classes against influenza

Answer 5

1. Amantidine
2. Neuraminidase inhibitor
3. Polymerase inhibitor

Question 6

What class of drug is oseltamivir? And what does it do?

Answer 6

Neuraminidase inhibitor

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

Question 7

What influenza vaccines are used in the UK?

Answer 7

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 8

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

Answer 8

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

Question 9

Most likely origin of COVID-19

What is a likely secondary host?

Answer 9

Horseshoe bats

Likely secondary host: pangolins

Question 10

Describe the genome of SARS-Cov2

Answer 10

Huge single-stranded RNA genome

Question 11

How does covid bind to cells to gain entry?

Answer 11

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

Question 12

How long after infection is covid infectious?

Answer 12

3 days

Question 13

From which day is COVID-19 symptomatic?

Answer 13

Day 5

Question 14

What is the time course of covid-19 infection?

Answer 14

Question 15

What is the predominant variant of COVID?

Answer 15

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 16

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

Answer 16

IL-6
D-dimer

Question 17

What benefit is remdesivir shown to have in coronavirus?

Answer 17

Shortens time to recovery

Question 18

In which patients is dexamethosone effective at reducing coronavirus death?

Answer 18

In those who are receiving oxygen

*dexatheasone is used in ITU setting

Question 19

Monocloncal antibodies and small molecule inhibitors for covid

Answer 19

Monoclonal: Regeneron, Sotrovimab

Small molecules:

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

Question 20

Natural reservoir of influenza A virus

Answer 20

• 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 21

How does influenza enter the human cell and spread?

Answer 21

• 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 22

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

Answer 22

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 23

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

Answer 23

Not in animal reservoirs

Do not exist in antigenically different form to human variants

→ humans can recognise and act against them

Question 25

Can you use influenza drugs in combination?

Answer 25

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

Question 28

What famiy is influenza virus from?

Answer 28

Orthomyxoviridiae

Question 29

Structure of influenza virus?

Answer 29

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

Question 30

3 key properties of a pandemic virus

Answer 30

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

Question 31

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

Answer 31

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

3. Influenza B (peaks March)

Question 32

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

What about the one given to children?

Answer 32

Purified fraction with HA and NA of inactivated virus

Children: live attenuated vaccine

Question 33

What is the natural reservoir of influenza virus?

Answer 33

Ducks

Question 34

Why is human-human transmission of bird flu difficult?

Answer 34

Bird flue - H5N1

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

Question 35

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

Answer 35

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 36

What does H5N1 actually mean?

Answer 36

h= haemagglutinin

n= neuraminidase

Question 37

What is antigenic drift?

Answer 37

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

eg thsi is what happens between the different strains of influenza

Question 38

What is antigenic shift?

Answer 38

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 40

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

Answer 40

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 41

What was unusula about the swine flu pandemic?

Answer 41

elderly people were relatively spared

Question 42

How does amantadine work? why is there resistance?

Answer 42

targets m2 ion channel

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

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

Question 43

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

Answer 43

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 45

What type of vaccine is SARS COV2 vaccine?

Answer 45

mRNA vaccines encoding stabilized spike