Chicken anemia virus VP1 negatively regulates type I interferon via targeting interferon regulatory factor 7 of the DNA-sensing pathway

文献类型： 外文期刊

第一作者： Liu, Xuelan

作者： Liu, Xuelan;Xi, Dexian;Xu, Aiyun;Wang, Yuan;Song, Tao;Ma, Tiantian;Xu, Fazhi;Li, Jinnian;Liu, Xuelan;Li, Jinnian;Ye, Hong;Li, Lin;Sun, Feifei;Zheng, Hao

作者机构：

关键词： chicken anemia virus; type I interferon; VP1; interferon regulatory factor 7; dimerization

期刊名称：POULTRY SCIENCE （ 影响因子：4.4； 五年影响因子：4.4 ）

ISSN： 0032-5791

年卷期： 2023 年 102 卷 1 期

页码：

收录情况： SCI

摘要： The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) sig-naling pathway plays a vital role in sensing viral DNA in the cytosol, stimulating type I interferon (IFN) produc-tion and triggering the innate immune response against DNA virus infection. However, viruses have evolved effective inhibitors to impede this sensing pathway. Chicken anemia virus (CAV), a nonenveloped ssDNA virus, is a ubiquitous pathogen causing great economic losses to the poultry industry globally. CAV infection is reported to downregulate type I IFN induction. How-ever, whether the cGAS-STING signal axis is used by CAV to regulate type I IFN remains unclear. Our results demonstrate that CAV infection significantly elevates the expression of cGAS and STING at the mRNA level, whereas IFN-b levels are reduced. Furthermore, IFN-b activation was completely blocked by the structural protein VP1 of CAV in interferon stimulatory DNA (ISD) or STING-stimulated cells. VP1 was further confirmed as an inhibitor by interacting with interferon regulatory factor 7 (IRF7) by binding its C-terminal 143-492 aa region. IRF7 dimerization induced by TANK binding kinase 1 (TBK1) could be inhibited by VP1 in a dosedependent manner. Together, our study demonstrates that CAV VP1 is an effective inhibitor that interacts with IRF7 and antagonizes cGAS-STING pathwaymediated IFN-b activation. These findings reveal a new mechanism of immune evasion by CAV.

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