On April 6, 2016, researchers at Dr. Chunfu Zheng’s group published an article entitled “Herpes simplex virus type 1 serine protease VP24 blocks DNA sensing signal pathway by abrogating IRF3 activation” in Journal of Virology. This is the first identified HSV-1 protein involving in evasion of host innate antiviral immune response mediated by DNA sensor signaling pathway.
The serine protease VP24 of HSV-1 is essential for formation and maturation of capsids. During capsid maturation, the UL26-encoded protease processes itself to release the N-terminal protease domain VP24. However, the role of VP24 in immune evasion is still unknown. In this study, VP24 was shown for the first time to dampen interferon stimulated DNA (ISD) and cGAS-STING mediated IFN-β production. The underlying molecular mechanism is that VP24 abrogated the interaction between TBK1 and IRF3 thus inhibiting the activation of IRF3 through blocking its phosphorylation and dimerization. Findings from this study reveals a new function of VP24 and a novel strategy by which HSV-1 subverts the host antiviral immune responses mediated by cGAS-STING DNA sensing signal pathway, which may contribute the pathogenesis of HSV-1 infection.
Ms. Dandan Zhang and Ms. Chenhe Su are the co-first authors; Prof. Chunfu Zheng is the corresponding author. Work in the Zheng laboratory relevant to this article was supported by grants from the National Natural Science Foundation of China (81371795 and 81571974) and Innovative Research Team in Soochow University (PCSIRT, IRT1075).