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KMID : 0381120230450060711
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Genes and Genomics
2023 Volume.45 No. 6 p.711 ~ p.781
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Host factor TNK2 is required for influenza virus infection
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Ao Zhou
Wenhua Zhang
Baoxin Wang
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Abstract
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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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KEYWORD
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TNK2, CRISPR, Autophagy, Lysosome, Influenza virus
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