Ashley Flashcards
(20 cards)
What is the subtype of Influenza A determined by
- Neuraminidase (NA)
- Hemagglutinin (HA)
NA role
- facilitates release of virions through cleavage
- removes sialicyl residues from the membrane of infected cells and from viral membranes to enable budding and release of newly synthesised virus particles
HA
- binds to sialylated host cell receptors and mediates membrane fusion
- mediates viral entry
IAV host range
- broad
- mostly in aquatic birds but have seen outbreaks into pigs which allows for adaption into humans and spillovers into poultry
Evolutionary mechanisms which allow for a broad host range
- Reassortment = 2 viruses infect and the same host cells and combine genome resulting in a new virus
- Genetic mutations
When do zoonotic outbreaks usually occur
when there is an increased need for food leading to intensified agriculture
LPAI
- low pathogenic
- causes no signs of disease or mild disease in infected poultry
- monobasic = cleaved by trypsin like proteases in respiratory and intestinal
HPAI
- high pathogenic
- causes severe disease and high mortality in infected poultry
- polybasic = cleavage site can be cleaved by ubiquitous proteases
What caused the creation of HPAI H5N1
continued reassortment between H5N1 and LPAI allowing for emergence into mammalian species
Difficulties in H5N1 HA infecting humans
- HA binds a-2,3 linked sialic acid for cell entry
- this is found in the lower respiratory tract so it is hard for the virus to reach
- a-2,6 linked is in the upper respiratory so would be easier for virus to reach
Mechanism of HPAI H5N1 causing severe disease into the lower respiratory tract of monkeys
disruption of epithelial barrier function in alveolar epithelial cells
Current routes of human transmission
- direct contact
- milk splashing into eye
What is a pandemic
an outbreak of infectious disease that occurs over a wide geographical area and is of high prevalence
What are characteristics required for a pandemic causing strain
- antigenically novel = no existing immunity in the human population
- causes severe disease
- sustained human to human transmission
What changes would be needed for HPAI H5N1 to cause efficient human to human transmission
- mutations in viral polymerase proteins to be compatible with mammalian host machinery
- mutations to switch from a2,3 to a2,6 allowing for effective HA binding and thus viral entry
- HA has to tolerate acidic microenvironment of airborne particles and respiratory secretions
What mutations have been shown to switch a2,3 to a2,6
- Q226L substitution and loss of glycosylation site near the receptor-binding site
Summary of H5N1 pandemic risk
- Antigenically novel > hasnt circulated in the human population
- potential protection offered by N1 from seasonal H1N1
- adaptation of viral polymerase possible
- no isolated H5N1 with a2,6 receptor specificity
- no human to human transmission
- current host range limits opportunities for reassortment with other mammalian adapted viruses
Countermeasures
- vaccination
- PPE
- antivirals
- Surveillance of species
Seasonal flu vaccines making humans serologically prepared for H5N1 - Sanz Munoz et al. 2024
- seasonal vaccines increased H5N1 neutralising antibodies by 12-15% of those primed by H3N2/H1N1
- antibody levels declined by 6 months
H1N1 provides immunity for H5N1 in ferrets - Le Sage et al. 2025
- infected H1N1 recovered ferrets with H5N
- identified cross-neutralising antibodies against H5N1 > NA
- Ferrets with H1N1 immunity showed decreased levels of viral replication limited to the respiratory tract, no detectable H5N1 in nasal washes, increased survival
- immunologically naive ferrets had more severe clinical signs
