tetano
Editor, Senior Moderator
PLoS Pathog
. 2021 Dec 3;17(12):e1010098.
doi: 10.1371/journal.ppat.1010098. eCollection 2021 Dec.
H9N2 virus-derived M1 protein promotes H5N6 virus release in mammalian cells: Mechanism of avian influenza virus inter-species infection in humans
Fangtao Li[SUP] 1 [/SUP], Jiyu Liu[SUP] 1 [/SUP], Jizhe Yang[SUP] 1 [/SUP], Haoran Sun[SUP] 1 [/SUP], Zhimin Jiang[SUP] 1 [/SUP], Chenxi Wang[SUP] 1 [/SUP], Xin Zhang[SUP] 1 [/SUP], Yinghui Yu[SUP] 1 [/SUP], Chuankuo Zhao[SUP] 1 [/SUP], Juan Pu[SUP] 1 [/SUP], Yipeng Sun[SUP] 1 [/SUP], Kin-Chow Chang[SUP] 2 [/SUP], Jinhua Liu[SUP] 1 [/SUP], Honglei Sun[SUP] 1 [/SUP]
Affiliations
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.
. 2021 Dec 3;17(12):e1010098.
doi: 10.1371/journal.ppat.1010098. eCollection 2021 Dec.
H9N2 virus-derived M1 protein promotes H5N6 virus release in mammalian cells: Mechanism of avian influenza virus inter-species infection in humans
Fangtao Li[SUP] 1 [/SUP], Jiyu Liu[SUP] 1 [/SUP], Jizhe Yang[SUP] 1 [/SUP], Haoran Sun[SUP] 1 [/SUP], Zhimin Jiang[SUP] 1 [/SUP], Chenxi Wang[SUP] 1 [/SUP], Xin Zhang[SUP] 1 [/SUP], Yinghui Yu[SUP] 1 [/SUP], Chuankuo Zhao[SUP] 1 [/SUP], Juan Pu[SUP] 1 [/SUP], Yipeng Sun[SUP] 1 [/SUP], Kin-Chow Chang[SUP] 2 [/SUP], Jinhua Liu[SUP] 1 [/SUP], Honglei Sun[SUP] 1 [/SUP]
Affiliations
- PMID: 34860863
- DOI: 10.1371/journal.ppat.1010098
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.
