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

Autoři: Louise H. Moncla aff001;  Trevor Bedford aff001;  Philippe Dussart aff003;  Srey Viseth Horm aff003;  Sareth Rith aff003;  Philippe Buchy aff004;  Erik A. Karlsson aff003;  Lifeng Li aff005;  Yongmei Liu aff005;  Huachen Zhu aff005;  Yi Guan aff005;  Thomas C. Friedrich aff007;  Paul F. Horwood aff003
Působiště autorů: Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America aff001;  University of Washington, Seattle, Washington, United States of America aff002;  Virology Unit, Institut Pasteur du Cambodge, Institut Pasteur International Network, Phnom Penh, Cambodia aff003;  GlaxoSmithKline, Vaccines R&D, Singapore, Singapore aff004;  Joint Influenza Research Centre (SUMC/HKU), Shantou University Medical College, Shantou, People's Republic of China aff005;  State Key Laboratory of Emerging Infectious Diseases/Centre of Influenza Research, School of Public Health, The University of Hong Kong, Hong Kong, SAR, People's Republic of China aff006;  Department of Pathobiological Sciences, University of Wisconsin School of Veterinary Medicine, Madison, WI, United States of America aff007;  Wisconsin National Primate Research Center, Madison, WI, United States of America aff008;  College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, Australia aff009
Vyšlo v časopise: Quantifying within-host diversity of H5N1 influenza viruses in humans and poultry in Cambodia. PLoS Pathog 16(1): e32767. doi:10.1371/journal.ppat.1008191
Kategorie: Research Article
doi: 10.1371/journal.ppat.1008191


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.

Klíčová slova:

Animal phylogenetics – Cell binding – Ducks – H5N1 – Microbial mutation – Mutation detection – Respiratory infections – Viral replication


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