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

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