Circovirus Rep evades immune restriction by disrupting cGAS oligomerization and phase separation

文献类型： 外文期刊

第一作者： Yin, Hongyan

作者： Yin, Hongyan;Zhao, Zhenchao;Yuan, Ye;Li, Minjie;Chai, Lvye;Qu, Weiyu;Ya, Yan;Li, Xin;Yin, Hongyan;Zhao, Zhenchao;Yuan, Ye;Li, Minjie;Chai, Lvye;Qu, Weiyu;Ya, Yan;Li, Xin;Wang, Haiwei

作者机构：

期刊名称：PLOS PATHOGENS （ 影响因子：4.9； 五年影响因子：5.4 ）

ISSN： 1553-7366

年卷期： 2025 年 21 卷 6 期

页码：

收录情况： SCI

摘要： Cyclic GMP-AMP synthase (cGAS) is a key sensor of double-stranded DNA (dsDNA), initiating oligomerization and phase separation to drive immune responses against pathogens and endogenous damage. Porcine circovirus (PCV) induces immunosuppression, heightening susceptibility to secondary infections, but the underlying mechanisms remain unclear. Here, we report PCV type 2d (PCV2d) infection fails to induce type I interferons (IFN-I) and significantly suppresses IFN-I production upon poly (dA:dT) stimulation in a dose-dependent manner. Mechanistically, the replication-related protein (Rep) proteins of PCV2, PCV3 and PCV4 inhibit cGAS-mediated IFN-I induction by competitively binding dsDNA, thereby disrupting cGAS oligomerization and phase separation. Interestingly, Rep also suppresses mitochondria DNA-induced cGAS activation. We further identify Rep residues Q12 and R199-W202 as key regions facilitating dsDNA binding. Our findings reveal a previously unrecognized mechanism by which circovirus Rep antagonizes cGAS activation, providing new insights into PCV-induced immunosuppression.

分类号：

  • 相关文献
作者其他论文 更多>>

微信小程序