Herpes simplex virus (HSV) is the main cause of viral encephalitis in the Western world, and the type I interferon (IFN) system is important for antiviral control in the brain. Here, we have compared Ifnb induction in mixed murine brain cell cultures by a panel of HSV1 mutants, each devoid of one mechanism to counteract the IFN-stimulating cGAS–STING pathway. We found that a mutant lacking the deubiquitinase (DUB) activity of the VP1-2 protein induced particularly strong expression of Ifnb and IFN-stimulated genes. HSV1 ΔDUB also induced elevated IFN expression in murine and human microglia and exhibited reduced viral replication in the brain. This was associated with increased ubiquitination of STING and elevated phosphorylation of STING, TBK1, and IRF3. VP1-2 associated directly with STING, leading to its deubiquitination. Recruitment of VP1-2 to STING was dependent on K150 of STING, which was ubiquitinated by TRIM32. Thus, the DUB activity of HSV1 VP1-2 is a major viral immune-evasion mechanism in the brain.

Nasopharyngeal carcinoma (NPC) is one of the most common tumors occurring in China and Southeast Asia. Etiology of NPC seems to be complex and involves many determinants, one of which is Epstein-Barr virus (EBV) infection. Although evidence demonstrates that EBV infection plays a key role in NPC carcinogenesis, the exact relationship between EBV and dysregulation of signaling pathways in NPC needs to be clarified. This review focuses on the interplay between EBV and NPC cells and the corresponding signaling pathways, which are modulated by EBV oncoproteins and non-coding RNAs. These altered signaling pathways could be critical for the initiation and progression of NPC.

No abstract