The Molecular Mechanism of Herpes Simplex Virus 1 UL31 in Antagonizing the Activity of IFN-β
Lan Gong, Xiaowen Ou, Hu Li, Jiayi Zhong, Jingjing Li, Shenyu Deng, Bolin Li, Lingxia Pan, Liding Wang, Xuejun Hong, Wenqi Luo, Qiyuan Zeng, Jie Zan, Tao Peng, Mingsheng Cai, Meili Li
Abstract
The innate immune system is the first line of host defense against the invasion of pathogens. Among its mechanisms, IFN-I is an essential cytokine in the antiviral response, which can help the host eliminate a virus. HSV-1 is a double-stranded DNA virus that can cause herpes and establish a lifelong latent infection, due to its possession of multiple mechanisms to escape host innate immunity. In this study, we illustrate for the first time that the HSV-1-encoded UL31 protein has a negative regulatory effect on IFN-β production by blocking the dimerization and nuclear translocation of IRF3, as well as promoting the K48-linked polyubiquitination and degradation of both IKKi and IRF3. This study may be helpful for fully understanding the pathogenesis of HSV-1.