Microbiology 19 - Influenza and Covid-19 Flashcards
(27 cards)
what proteins does influenza have on its surface?
Haemagglutinin (HA) and Neuraminidase (NA)
HA = virus entry into cells; NA = virus exit from cells
What drives zoonosis of influenza viruses from wild water fowl?
Antigenic drift
What must a mutation change to produce a pandemic-producing virus ?
Transmissibility between humans
Antigenic novelty
What is the ANP32 co factor required for?
essential for influenza polymerase activity
How does influenza cross over from birds to humans?
1. PB2 mutation
Specific mutation that can enable bird flu to cross into humans – PB2 627K
2. reassortment
antigenic shift:
single cell infected by both human and bird virus
they shuffle their RNA → production of a bird virus that can infect a human
but not sufficient for pandemic - needs further mutations in HA for airborne transmission between people
Why is there incompatibility between avian flu viruses and the human host?
polymerase activity different in birds - extra 33 aa exon in ANP32
How does influenza transmit between people?
- different receptor binding
- virion stability
How is receptor binding different in birds and humans?
red (avian) unable to use sialic acid binding in human resp tract
blue (human) have mutated HA spike → acquire affinity for human receptors (a2,3 → a2,6)
avian virus can bind a2-3 receptors → only in LRT → severe pneumonia (cannot enter URT)
Recall the process of influenza A cleavage
- Viral spike proteins (most important is haemaglutinnin - HA)
- Protease required to cleave HA is only found in airway (Human Airway Tryptase)
- HAT cleaves influenza A at a specific site
How does virion stability impact transmissibility between people?
influenza entry pH dependent + HA protein is pH sensitive (mildly acidic environment needed for entry)
as respiratory secretions travel through air → water evaporates → more concentrated → ↓pH
avian viruses inactivated in low pH → cannot survive in airborne droplets → need further HA mutation for stability in low pH
What is the mechanism of action of amantidine, and what is it used for?
Targets M2 ion channel
Resistance from a single amino acid mutation in M2 (S31N)
Does NOT work against influenza B, pH1N1 or seasonal H3N2
How do neuraminidase inhibitors work?
NA cleaves sialic acid → virus can leave
blocking NA → virus will stay tethered and cannot replicate in other cells
What class of drug is oseltamivir - Tamiflu?
Neuraminidase inhibitor
what is an example of polymerase Inhibitors
Baloxavir - inhibits PA endonuclease
what type of flu vaccine is given to those at greater risk of flu complications?
a purified fraction containing HA and NA of an inactivated virus
Short term strain specific immunity mediated by antibody to HA head
Describe the genome of SARS-Cov2
Huge single-stranded RNA genome
How does covid bind to cells to gain entry?
Via ACE2
What is Nsp14, and why is it important to the covid genome?
It’s a proof-reading exonuclease - which is unusual for an RNA virus
How long after infection is covid infectious?
3 days
Recall 2 important factors that will be at elevated serum levels in covid infection, and can be useful clinically?
IL-6
D-dimer
What benefit is remdesivir shown to have in coronavirus?
Shortens time to recovery
In which patients is dexamethosone effective at reducing coronavirus death?
In those who are receiving oxygen and ventilated
if ITU → viral replication not the problem → immunopathology
Which monoclonal is being used to treat coronavirus?
Tociluzmab - anti-IL6
regeneron
Sotrovimab
what type of flu vaccine is given to children?
live attenuated vaccine [intranasal]
Broader more cross-reactive immunity including a cellular response
