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H9N2 virus-derived M1 protein promotes H5N6 virus release in mammalian cells: Mechanism of avian influenza virus inter-species infection in humans

Li, Fangtao; Liu, Jiyu; Yang, Jizhe; Sun, Haoran; Jiang, Zhimin; Wang, Chenxi; Zhang, Xin; Yu, Yinghui; Zhao, Chuankuo; Pu, Juan; Sun, Yipeng; Chang, Kin-Chow; Liu, Jinhua; Sun, Honglei

H9N2 virus-derived M1 protein promotes H5N6 virus release in mammalian cells: Mechanism of avian influenza virus inter-species infection in humans Thumbnail


Authors

Fangtao Li

Jiyu Liu

Jizhe Yang

Haoran Sun

Zhimin Jiang

Chenxi Wang

Xin Zhang

Yinghui Yu

Chuankuo Zhao

Juan Pu

Yipeng Sun

KIN-CHOW CHANG KIN-CHOW.CHANG@NOTTINGHAM.AC.UK
Professor of Veterinary Molecular Medicine

Jinhua Liu

Honglei Sun



Contributors

Daniel R. Perez
Editor

Abstract

H5N6 highly pathogenic avian influenza virus (HPAIV) clade 2.3.4.4 not only exhibits unprecedented intercontinental spread in poultry, but can also cause serious infection in humans, posing a public health threat. Phylogenetic analyses show that 40% (8/20) of H5N6 viruses that infected humans carried H9N2 virus-derived internal genes. However, the precise contribution of H9N2 virus-derived internal genes to H5N6 virus infection in humans is unclear. Here, we report on the functional contribution of the H9N2 virus-derived matrix protein 1 (M1) to enhanced H5N6 virus replication capacity in mammalian cells. Unlike H5N1 virus-derived M1 protein, H9N2 virus-derived M1 protein showed high binding affinity for H5N6 hemagglutinin (HA) protein and increased viral progeny particle release in different mammalian cell lines. Human host factor, G protein subunit beta 1 (GNB1), exhibited strong binding to H9N2 virus-derived M1 protein to facilitate M1 transport to budding sites at the cell membrane. GNB1 knockdown inhibited the interaction between H9N2 virus-derived M1 and HA protein, and reduced influenza virus-like particles (VLPs) release. Our findings indicate that H9N2 virus-derived M1 protein promotes avian H5N6 influenza virus release from mammalian, in particular human cells, which could be a major viral factor for H5N6 virus cross-species infection.

Citation

Li, F., Liu, J., Yang, J., Sun, H., Jiang, Z., Wang, C., …Sun, H. (2021). H9N2 virus-derived M1 protein promotes H5N6 virus release in mammalian cells: Mechanism of avian influenza virus inter-species infection in humans. PLoS Pathogens, 17(12), Article e1010098. https://doi.org/10.1371/journal.ppat.1010098

Journal Article Type Article
Acceptance Date Nov 5, 2021
Online Publication Date Dec 3, 2021
Publication Date Dec 3, 2021
Deposit Date Dec 6, 2021
Publicly Available Date Dec 6, 2021
Journal PLoS Pathogens
Print ISSN 1553-7366
Electronic ISSN 1553-7374
Publisher Public Library of Science
Peer Reviewed Peer Reviewed
Volume 17
Issue 12
Article Number e1010098
DOI https://doi.org/10.1371/journal.ppat.1010098
Keywords Virology; Genetics; Molecular Biology; Immunology; Microbiology; Parasitology
Public URL https://nottingham-repository.worktribe.com/output/6908186
Publisher URL https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010098

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