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KRT10 plays an important role in the release of viral genome from endosomes during H9N2 subtype AIV replication in HeLa cells

文献类型： 外文期刊

作者： Huang, Xiangyu 1 ; Yin, Guihu 1 ; Zhou, Bin 1 ; Cai, Yiqin 1 ; Hu, Jianing 1 ; Huang, Jingwen 3 ; Chen, Zili 4 ; Liu, Qingtao 2 ; Feng, Xiuli 1 ;

作者机构： 1.Nanjing Agr Univ, Coll Vet Med, Key Lab Anim Microbiol, Chinas Minist Agr, Nanjing 210095, Peoples R China

2.Jiangsu Acad Agr Sci, Inst Vet Med, Key Lab Vet Biol Engn & Technol, Minist Agr, Nanjing 210014, Peoples R China

3.Nanjing Agr Univ, Coll Vet Med, MOE Joint Int Res Lab Anim Hlth & Food Safety, Nanjing 210095, Peoples R China

4.Rudong Agr & Rural Affairs Bur, Agr Comprehens Law Enforcement Brigade Rudong, Rudong 226400, Peoples R China

关键词： Keratin 10; Avian Influenza Virus; Late endosomes; lysosomes; Trafficking; Viral replication; NS2 protein; Virus particle release

期刊名称：VETERINARY MICROBIOLOGY （ 影响因子：3.3； 五年影响因子：3.5 ）

ISSN： 0378-1135

年卷期： 2023 年 284 卷

页码：

收录情况： SCI

摘要： The infection and replication of avian influenza virus (AIV) in host cells is a complex biological process that involves the transport of viral genes through the host cell's transport systems. Actin, microtubules and vimentin are known to facilitate transport of endosomes to the perinuclear region, but the biological role of Keratin, another intermediate filament, in viral transport during AIV replication is not well understood. In this study, the viral NS2 protein was used as the target protein to identify the potential interacting proteins following GSTPulldown method and protein mass spectrometry. It was discovered that Keratin10 interacted with NS2. Subsequently, it was found AIV infection did not affect the gene level or protein level of keratin10 in HeLa cells, but when Keratin10 was knocked down, the expressions of viral NP mRNA and protein were reduced, and the generation of offspring virus also was also decreased. Furthermore, in early viral infection, Keratin10 could aggregate and co-localize with NP proteins, suggesting that Keratin10 might be connected to early viral transport. Additionally, it was demonstrated that Keratin10 co-localized with Lamp1 and that AIV particles were trapped in late endosomes/Lysosomes after Keratin10 was knocked down. Finally, it was discovered that the knocking down Keratin10 in HeLa cells led to an increase in the acidic pH of endosomes and lysosomes, which prevented AIV from undergoing fusion and uncoating, and then inhibited the process of the viral infection. Overall, the results suggested that Keratin10 might play the critical role in the release of vRNPs from LEs/Ls and can affect the generation of offspring virus. The study provides the novel insights into the role of Keratin10 in the process of AIV infection and transmission, which may have implications for developing new strategies to against AIV infections.

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