Quantifying within-host diversity of H5N1 influenza viruses in humans and poultry in Cambodia

Moncla, Lousie H., Bedford, Trevor, Dussart, Philippe, Horm, Srey Viseth, Rith, Sareth, Buchy, Philippe, Karlsson, Erik A., Li, Lifeng, Liu, Yongmei, Zhu, Huachen, Guan, Yi, Friedrich, Thomas C., and Horwood, Paul F. (2020) Quantifying within-host diversity of H5N1 influenza viruses in humans and poultry in Cambodia. PLoS Pathogens, 16 (1). e1008191.

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Abstract

Avian influenza viruses (AIVs) periodically cross species barriers and infect humans. The likelihood that an AIV will evolve mammalian transmissibility depends on acquiring and selecting mutations during spillover, but data from natural infection is limited. We analyze deep sequencing data from infected humans and domestic ducks in Cambodia to examine how H5N1 viruses evolve during spillover. Overall, viral populations in both species are predominated by low-frequency (<10%) variation shaped by purifying selection and genetic drift, and half of the variants detected within-host are never detected on the H5N1 virus phylogeny. However, we do detect a subset of mutations linked to human receptor binding and replication (PB2 E627K, HA A150V, and HA Q238L) that arose in multiple, independent humans. PB2 E627K and HA A150V were also enriched along phylogenetic branches leading to human infections, suggesting that they are likely human-adaptive. Our data show that H5N1 viruses generate putative human-adapting mutations during natural spillover infection, many of which are detected at >5% frequency within-host. However, short infection times, genetic drift, and purifying selection likely restrict their ability to evolve extensively during a single infection. Applying evolutionary methods to sequence data, we reveal a detailed view of H5N1 virus adaptive potential, and develop a foundation for studying host-adaptation in other zoonotic viruses.

Item ID: 62250
Item Type: Article (Research - C1)
ISSN: 1553-7374
Copyright Information: © 2020 Moncla et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funders: US Agency for International Development
Projects and Grants: Grant no. AID-442-G-14-00005
Date Deposited: 17 Mar 2020 22:16
FoR Codes: 07 AGRICULTURAL AND VETERINARY SCIENCES > 0707 Veterinary Sciences > 070712 Veterinary Virology @ 100%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970107 Expanding Knowledge in the Agricultural and Veterinary Sciences @ 100%
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