Speaker
Description
In wild waterfowl avian influenza viruses (AIV) primarily replicate in the gastrointestinal tract and are shed into the environment at large quantities facilitating transmission to domestic poultry. Continuous circulation of H5 and H7 AIVs in domestic poultry may favour the evolution of highly pathogenic AIVs (HPAIV). To understand the adaptation process of AIV in poultry, we experimentally infected chickens via the intratracheal route with a number of low-pathogenic AIV (LPAIV) H5Nx and H7Nx isolates from wild waterfowl. While most H7Nx LPAIV were transmitted to contact animals without prior adaptation, none of the H5Nx LPAIV was passed to the sentinels. Interestingly, H5N1 and H5N8 HPAIV isolates were not transmitted to sentinel chickens when the HA proteolytic cleavage site was changed from a polybasic to a monobasic motif. Genetic reassortment of a non-transmittable H5N1 virus with either a transmittable H7N7 virus or a chicken-adapted H5N2 virus revealed that the hemagglutinin (HA) is critical for efficient virus shedding and transmission. Mutations in HA changing the pH threshold of fusion, the proteolytic cleavage site or potential glycosylation sites did not enhance virus transmission. However, recombinant H5N1 harboring the globular HA head domain from a chicken-adapted H5N2 was efficiently transmitted. Mutational analysis demonstrated that adaptations in the receptor-binding pocket (130-loop, 190-helix, and 220-loop) of HA are critical for H5 virus transmission in chickens. These findings suggest that duck-origin H5 viruses exhibit different receptor-binding activities than chicken-adapted viruses. Whether these adaptive mutations have an impact on receptor specificity or receptor affinity is currently under investigation.
| Choose secondary Session | Evolution and Emerging viruses |
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| Choose primary session | Pathogenesis |
