Proteomic analysis reveals zinc-finger CCHC-type containing protein 3 as a factor inhibiting virus infection by promoting innate signaling

文献类型： 外文期刊

第一作者： Chen, Xiaoyong

作者： Chen, Xiaoyong;Li, Ziwei;Wang, Shuaiwei;Zhao, Yan;Chen, Xiaoyong;Tong, Guangzhi;Chen, Keyuan

作者机构：

关键词： Proteomic analysis; Cellular factor; Influenza virus; Zinc-finger CCHC-type containing protein 3; Innate signaling

期刊名称：VIRUS RESEARCH （ 影响因子：5.0； 五年影响因子：4.0 ）

ISSN： 0168-1702

年卷期： 2022 年 319 卷

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收录情况： SCI

摘要： Influenza a virus exploits host machinery to benefit its replication in host cells. Knowledge of host factors reveals the complicated interaction and provides potential targets for antiviral treatment. Here, instead of the traditional proteomic analysis, we employed a 4D label free proteomic method to identify cellular factors in A549 cells treated with avian H9N2 virus. We observed that 425 proteins were upregulated and 502 proteins were downregulated. Western blotting and quantitative real-time PCR results showed that the zinc-finger CCHC-type containing protein 3 (ZCCHC3) levels were markedly induced by H9N2 infection. Transient expression assay showed that ZCCHC3 expression decreased NP protein levels and viral titers, whereas knockdown of ZCCHC3 enhanced viral growth. Specifically, ZCCHC3 promoted the expression of IFN-ss, leading to the increased transcription of IFN downstream antiviral factors. Surprisingly, viral NS1 protein was able to antagonize the antiviral effect of ZCCHC3 by downregulating IFN-ss. Eventually, we observed that chicken finger CCCH-type containing protein 3, named ZC3H3, could also suppress the replication of H9N2 virus and the coronavirus-infectious bronchitis virus (IBV) in DF-1 cells. Together, our results showed the cellular proteomic response to H9N2 infection and identified ZCCHC3 as a novel antiviral factor against H9N2 infection, contributing to the understanding of host-virus interaction.

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