Collective interactions augment influenza A virus replication in a host-dependent manner.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101674869 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2058-5276 (Electronic) Linking ISSN: 20585276 NLM ISO Abbreviation: Nat Microbiol Subsets: MEDLINE

Original Publication: [London] : Nature Publishing Group, [2016]-

Host-Pathogen Interactions/*physiology ; Influenza A virus/*genetics ; Influenza A virus/*physiology ; Virus Replication/*genetics ; Virus Replication/*physiology; Animals ; Birds ; Chickens ; Coturnix ; Disease Models, Animal ; Dogs ; Female ; Genome, Viral ; Guinea Pigs ; Host Specificity ; Humans ; Influenza A Virus, H9N2 Subtype/genetics ; Influenza in Birds/virology ; Influenza, Human/virology ; Madin Darby Canine Kidney Cells ; Orthomyxoviridae Infections/virology

Infection with a single influenza A virus (IAV) is only rarely sufficient to initiate productive infection. Instead, multiple viral genomes are often required in a given cell. Here, we show that the reliance of IAV on multiple infection can form an important species barrier. Namely, we find that avian H9N2 viruses representative of those circulating widely at the poultry-human interface exhibit acute dependence on collective interactions in mammalian systems. This need for multiple infection is greatly reduced in the natural host. Quantification of incomplete viral genomes showed that their complementation accounts for the moderate reliance on multiple infection seen in avian cells but not the added reliance seen in mammalian cells. An additional form of virus-virus interaction is needed in mammals. We find that the PA gene segment is a major driver of this phenotype and that both viral replication and transcription are affected. These data indicate that multiple distinct mechanisms underlie the reliance of IAV on multiple infection and underscore the importance of virus-virus interactions in IAV infection, evolution and emergence.

Comment in: Nat Rev Microbiol. 2020 Sep;18(9):475. (PMID: 32669680)

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Date Created: 20200708 Date Completed: 20201117 Latest Revision: 20220422

20231215

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10.1038/s41564-020-0749-2

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