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        Host factor TNK2 is required for influenza virus infection

        Zhou Ao,Zhang Wenhua,Wang Baoxin 한국유전학회 2023 Genes & Genomics Vol.45 No.6

        Background Host factors are required for Influenza virus infection and have great potential to become antiviral target. Objective Here we demonstrate the role of TNK2 in influenza virus infection. CRISPR/Cas9 induced TNK2 deletion in A549 cells. Methods CRISPR/Cas9-mediated deletion of TNK2. Western blotting and qPCR was used to measure the expression of TNK2 and other proteins. Results CRISPR/Cas9-mediated deletion of TNK2 decreased the replication of influenza virus and significantly inhibited the ex-pression of viral proteins and TNK2 inhibitors (XMD8-87 and AIM-100) reduced the expression of influenza M2, while over-expression of TNK2 weakened the resistance of TNK2-knockout cells to influenza virus infection. Furthermore, a decrease of nuclear import of IAV in the infected TNK2 mutant cells was observed in 3 h post-infection. Interestingly, TNK2 deletion enhanced the colocalization of LC3 with autophagic receptor p62 and led to the attenuation of influenza virus-caused accumulation of autophagosomes in TNK2 mutant cells. Further, confocal microscopy visualization result showed that influenza viral matrix 2 (M2) was colocalized with Lamp1 in the infected TNK2 mutant cells in early infection, while almost no colocalization between M2 and Lamp1 was observed in IAV-infected wild-type cells. Moreover, TNK2 depletion also affected the trafficking of early endosome and the movement of influenza viral NP and M2. Conclusion Our results identified TNK2 as a critical host factor for influenza viral M2 protein trafficking, suggesting that TNK2 will be an attractive target for the development of antivirals therapeutics.

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