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

H9N2 virus-derived M1 protein promotes H5N6 virus release in mammalian cells: Mechanism of avian influenza virus inter-species infection in humans.
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H9N2病毒衍生的M1蛋白促进哺乳动物细胞中H5N6病毒的释放:禽流感病毒在人类种间感染的机制。

DOI:
10.1371/journal.ppat.1010098
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发表时间:
2021-12
期刊:
影响因子:
6.7
通讯作者:
Sun H
Sun H
中科院分区:
医学1区
文献类型:
--
作者:
Li F;Liu J;Yang J;Sun H;Jiang Z;Wang C;Zhang X;Yu Y;Zhao C;Pu J;Sun Y;Chang KC;Liu J;Sun H

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H5 N6高致病性禽流感病毒(HPAIV)进化枝不仅在家禽中表现出前所未有的洲际传播,而且还可导致人类严重感染,构成公共卫生威胁。2.3.4.4系统发育分析显示,40%(8/20)感染人类的H5 N6病毒携带H9 N2病毒衍生的内部基因。然而,H9 N2病毒衍生的内部基因对人类H5 N6病毒感染的确切贡献尚不清楚。在这里,我们报告的H9 N2病毒衍生的基质蛋白1(M1),以增强H5 N6病毒在哺乳动物细胞中的复制能力的功能贡献。与H5 N1病毒衍生的M1蛋白不同,H9 N2病毒衍生的M1蛋白显示出对H5 N6血凝素(HA)蛋白的高结合亲和力,并且在不同哺乳动物细胞系中增加病毒子代颗粒释放。人类宿主因子,G蛋白亚基β 1(GNB 1),表现出强结合H9 N2病毒衍生的M1蛋白,以促进M1运输到细胞膜上的出芽位点。GNB 1基因敲低抑制了H9 N2病毒源M1与HA蛋白的相互作用,并减少了流感病毒样颗粒(VLP)的释放。我们的研究结果表明,H9 N2病毒衍生的M1蛋白促进禽H5 N6流感病毒从哺乳动物,特别是人类细胞中释放,这可能是H5 N6病毒跨种属感染的主要病毒因素。已知H9 N2禽流感病毒(AIV)通过其内部基因与其他流行的AIV亚型(H5 N6、H7N9、H10 N8和H10 N3病毒)的重配而使得所产生的新型疫苗能够感染人类。然而,H9 N2病毒衍生的内部基因在人类感染中的确切作用仍然未知。在此,我们发现H9 N2病毒衍生的(而不是H5 N1病毒衍生的)M1蛋白显示出与宿主GNB 1蛋白的强相互作用,以增强M1蛋白转运到细胞膜上的出芽位点,从而促进子代病毒的释放,从而促进H5 N6抵抗剂感染人类细胞。
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. H9N2 avian influenza viruses (AIVs), through reassortment of their internal genes with other circulating AIVs subtypes (H5N6, H7N9, H10N8 and H10N3 viruses), are known to enable the resulting novel reassortants to infect humans. However, the precise roles of H9N2 virus-derived internal genes in human infection remain unknown. Here, we found that H9N2 virus-derived (but not H5N1 virus-derived) M1 protein showed strong interaction with host GNB1 protein to enhance M1 protein transport to budding sites at the cell membrane to promote progeny virus release, hence facilitating H5N6 reassortants to infect human cells.
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