tetano
Editor, Senior Moderator
J Med Virol
. 2025 Sep;97(9):e70592.
doi: 10.1002/jmv.70592. Ablations of Human and Murine TNK2/ACK1 Proteins Do Not Alter Influenza A Virus Infections In Vitro or In Vivo
Sisi Liu[SUP] 1 2 [/SUP], Yiqun Fang[SUP] 1 2 [/SUP], Lingyu Li[SUP] 1 2 [/SUP], Jingwen Huo[SUP] 1 2 [/SUP], Binyi Liu[SUP] 1 2 [/SUP], Jianhao Wang[SUP] 1 2 [/SUP], Jimin Xu[SUP] 1 2 [/SUP], Fangzhou Song[SUP] 3 [/SUP], Haiyu Li[SUP] 4 [/SUP], Hongbing Jiang[SUP] 1 2 [/SUP]
Affiliations
Tyrosine kinase non-receptor2 (TNK2) is a host protein involved in vesicular trafficking, cell spreading, migration, survival, and proliferation. TNK2 has been identified as a conserved host factor for the entry of several non-enveloped RNA viruses, such as Orsay virus in Caenorhabditis elegans and multiple picornaviruses in cells and mice. Although TNK2 was reported as required for influenza A virus infection in a genome-wide CRISPR screen, its role remains contentious as it was not identified in other screens. In this study, we comprehensively evaluated TNK2's function in IAV infection using in vitro and in vivo models. RNAi knockdown and CRISPR knockout of TNK2 in multiple cells showed no significant reduction in IAV infection. Similarly, primary lung fibroblasts and bone marrow-derived macrophages from Tnk2[SUP]-/-[/SUP] mice exhibited comparable infection to those from Tnk2[SUP]+/+[/SUP] mice. Moreover, Tnk2[SUP]-/-[/SUP] mice exhibited no differences in weight loss, survival, lung pathology, or viral load compared to those of Tnk2[SUP]+/+[/SUP] mice after IAV infection. Furthermore, the expression of interferon-β and interferon-stimulated genes were not significantly altered in Tnk2[SUP]-/-[/SUP] mice compared to that of Tnk2[SUP]+/+[/SUP] mice. Together, these results indicate that TNK2 is not a dominant host factor for IAV infection, suggesting it may not be a viable therapeutic target.
Keywords: CRISPR knockout; TNK2; host factors; influenza; mouse.
. 2025 Sep;97(9):e70592.
doi: 10.1002/jmv.70592. Ablations of Human and Murine TNK2/ACK1 Proteins Do Not Alter Influenza A Virus Infections In Vitro or In Vivo
Sisi Liu[SUP] 1 2 [/SUP], Yiqun Fang[SUP] 1 2 [/SUP], Lingyu Li[SUP] 1 2 [/SUP], Jingwen Huo[SUP] 1 2 [/SUP], Binyi Liu[SUP] 1 2 [/SUP], Jianhao Wang[SUP] 1 2 [/SUP], Jimin Xu[SUP] 1 2 [/SUP], Fangzhou Song[SUP] 3 [/SUP], Haiyu Li[SUP] 4 [/SUP], Hongbing Jiang[SUP] 1 2 [/SUP]
Affiliations
- PMID: 40905071
- DOI: 10.1002/jmv.70592
Tyrosine kinase non-receptor2 (TNK2) is a host protein involved in vesicular trafficking, cell spreading, migration, survival, and proliferation. TNK2 has been identified as a conserved host factor for the entry of several non-enveloped RNA viruses, such as Orsay virus in Caenorhabditis elegans and multiple picornaviruses in cells and mice. Although TNK2 was reported as required for influenza A virus infection in a genome-wide CRISPR screen, its role remains contentious as it was not identified in other screens. In this study, we comprehensively evaluated TNK2's function in IAV infection using in vitro and in vivo models. RNAi knockdown and CRISPR knockout of TNK2 in multiple cells showed no significant reduction in IAV infection. Similarly, primary lung fibroblasts and bone marrow-derived macrophages from Tnk2[SUP]-/-[/SUP] mice exhibited comparable infection to those from Tnk2[SUP]+/+[/SUP] mice. Moreover, Tnk2[SUP]-/-[/SUP] mice exhibited no differences in weight loss, survival, lung pathology, or viral load compared to those of Tnk2[SUP]+/+[/SUP] mice after IAV infection. Furthermore, the expression of interferon-β and interferon-stimulated genes were not significantly altered in Tnk2[SUP]-/-[/SUP] mice compared to that of Tnk2[SUP]+/+[/SUP] mice. Together, these results indicate that TNK2 is not a dominant host factor for IAV infection, suggesting it may not be a viable therapeutic target.
Keywords: CRISPR knockout; TNK2; host factors; influenza; mouse.