Quantifying within-host diversity of H5N1 influenza viruses in humans and poultry in Cambodia
| Autor: | Sareth Rith, Thomas C. Friedrich, Yongmei Liu, Paul F. Horwood, Louise H. Moncla, Erik A. Karlsson, Srey Viseth Horm, Philippe Dussart, Hongbo Zhu, Lifeng Li, Trevor Bedford, Philippe Buchy, Yi Guan |
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| Přispěvatelé: | Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), University of Washington [Seattle], Unité de Virologie / Virology Unit [Phnom Penh], Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), GlaxoSmithKline Vaccines [Singapore], GlaxoSmithKline [Headquarters, London, UK] (GSK), Shantou University [Shantou, China], The University of Hong Kong (HKU), University of Wisconsin-Madison, Wisconsin National Primate Research Center [Madison, WI] (WNPRC), James Cook University (JCU), The study was funded by the US Agency for International Development (grant No. AID-442-G-14-00005). |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Pulmonology
Gene Identification and Analysis [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics Phylogenetics and taxonomy Poultry Negative selection MESH: Animals Biology (General) H5N1 virus MESH: Phylogeny Phylogeny 0303 health sciences MESH: Influenza Human 030302 biochemistry & molecular biology Microbial Mutation Eukaryota virus diseases H5N1 3. Good health [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology Cell Binding Cell Physiology QH301-705.5 Immunology Microbiology Deep sequencing Evolution Molecular 03 medical and health sciences Viral Proteins Phylogenetics Genetics Humans Evolutionary Systematics Molecular Biology Mutation Detection Medicine and health sciences MESH: Humans Influenza A Virus H5N1 Subtype 030306 microbiology Organisms Viral replication Evolutionary biology Fowl Influenza in Birds Mutation Parasitology Immunologic diseases. Allergy RNA viruses animal diseases Waterfowl Adaptive potential Animal Phylogenetics medicine.disease_cause Data sequences Zoonoses Influenza A virus MESH: Ducks MESH: Evolution Molecular Pathology and laboratory medicine Data Management Medical microbiology Infectious Diseases Ducks Viruses Vertebrates Pathogens Cambodia Research Article Computer and Information Sciences MESH: Mutation MESH: Influenza A Virus H5N1 Subtype Biology Birds Single infection Genetic drift MESH: Influenza in Birds Virology Influenza Human medicine Influenza viruses Animals 030304 developmental biology Taxonomy Evolutionary Biology Biology and life sciences MESH: Cambodia Viral pathogens Cell Biology RC581-607 MESH: Viral Proteins Influenza A virus subtype H5N1 Viral Replication Microbial pathogens Amniotes Respiratory Infections Zoology Orthomyxoviruses |
| Zdroj: | PLoS Pathogens PLoS Pathogens, Public Library of Science, 2020, 16 (1), pp.e1008191. ⟨10.1371/journal.ppat.1008191⟩ PLoS Pathogens, Vol 16, Iss 1, p e1008191 (2020) |
| ISSN: | 1553-7366 1553-7374 |
| DOI: | 10.1101/683151 |
| Popis: | 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 (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. Author summary H5N1 avian influenza viruses can cross species barriers and cause severe disease in humans. H5N1 viruses currently cannot replicate and transmit efficiently among humans, but animal infection studies and modeling experiments have suggested that human adaptation may require only a few mutations. However, data from natural spillover infection has been limited, posing a challenge for risk assessment. Here, we analyze a unique dataset of deep sequence data from H5N1 virus-infected humans and domestic ducks in Cambodia. We find that well-known markers of human receptor binding and replication arise in multiple, independent humans. We also find that 3 mutations detected within-host are enriched along phylogenetic branches leading to human infections, suggesting that they are likely human-adapting. However, we also show that within-host evolution in both humans and ducks are shaped heavily by purifying selection and genetic drift, and that a large fraction of within-host variation is never detected on the H5N1 phylogeny. Taken together, our data show that H5N1 viruses do generate human-adapting mutations during natural infection. However, short infection times, purifying selection, and genetic drift may severely limit how much H5N1 viruses can evolve during the course of a single infection. |
| Databáze: | OpenAIRE |
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