PLoS Pathog. 2020 Jan 17;16(1):e1008191. doi: 10.1371/journal.ppat.1008191. [Epub ahead of print] Quantifying within-host diversity of H5N1 influenza viruses in humans and poultry in Cambodia.
Moncla LH1, Bedford T1,2, Dussart P3, Horm SV3, Rith S3, Buchy P4, Karlsson EA3, Li L5,6, Liu Y5,6, Zhu H5,6, Guan Y5,6, Friedrich TC7,8, Horwood PF3,9.
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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.
PMID: 31951644 DOI: 10.1371/journal.ppat.1008191
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