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Host factor TNK2 is required for influenza virus infection

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Abstract

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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Data availability

All data generated or analyzed during this study are included in this published article.

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Acknowledgements

This work was financially sponsored by NSFC (81902073), Key Laboratory of Animal Embryo Engineering and Molecular Breeding of Hubei Province (KLAEMB-2021-01) and Wuhan polytechnic university.

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Authors and Affiliations

  1. School of Animal Science and Nutritional Engineering, Laboratory of Genetic Breeding, Reproduction and Precision Livestock Farming, Wuhan Polytechnic University, Wuhan, 430023, Hubei, China

    Ao Zhou, Wenhua Zhang & Baoxin Wang

  2. Hubei Provincial Center of Technology Innovation for Domestic Animal Breeding, Hubei Wuhan, Hubei, 430023, China

    Ao Zhou, Wenhua Zhang & Baoxin Wang

Authors
  1. Ao Zhou
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  2. Wenhua Zhang
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  3. Baoxin Wang
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Contributions

All authors contributed to this manuscript and approved the final manuscript. AZ designed this project and did most of the experiments, analyzed and interpreted data, and contributed to the writing of the manuscript; WHZ analyzed and interpreted data; BXW made immunofluorescences; XD reviewed and modified this manuscript; AZ provided financial support; AZ designed the experiments, supervised the research and wrote the manuscript. All authors read and approved the final manuscript.

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Correspondence to Ao Zhou.

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Zhou, A., Zhang, W. & Wang, B. Host factor TNK2 is required for influenza virus infection. Genes Genom 45, 771–781 (2023). https://doi.org/10.1007/s13258-023-01384-8

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