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A systematic and flexible immunoregulatory network is required to ensure the proper outcome of antiviral immune signaling and maintain homeostasis during viral infection. Tumor necrosis factor-α-induced protein 8-like 2 (TIPE2), a novel immunoregulatory protein, has been extensively studied in inflammatory response, apoptosis, and cancer. However, the function of TIPE2 in antiviral innate immunity is poorly clarified. In this study, we reported that the expression of TIPE2 declined at the early period and then climbed up in macrophages under RNA virus stimulation. Knockout of TIPE2 in the macrophages enhanced the antiviral capacity and facilitated type I interferon (IFN) signaling after RNA viral infection both in vitro and in vivo . Consistently, overexpression of TIPE2 inhibited the production of type I IFNs and pro-inflammatory cytokines, and thus promoted the viral infection. Moreover, TIPE2 restrained the activation of TBK1 and IRF3 in the retinoic acid inducible gene-I (RIG-I)-like receptors (RLR) signaling pathway by directly interacting with retinoic acid inducible gene-I (RIG-I). Taken together, our results suggested that TIPE2 suppresses the type I IFN response induced by RNA virus by targeting RIG-I and blocking the activation of downstream signaling. These findings will provide new insights to reveal the immunological function of TIPE2 and may help to develop new strategies for the clinical treatment of RNA viral infections., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zou, Li, Zhou, Li, Pan, Lai, Wang, Zhang, Wang, Song and Zhang.)

MicroRNAs are short, non-coding RNAs that have been shown to regulate a wide range of biological processes, including host antiviral immune responses. In the present study, microRNA-92a (miR-92a) was identified as a negative regulator in macrophage-mediated antiviral responses. Overexpression of miR-92a decreases vesicular stomatitis virus (VSV)-induced production of type-I IFNs and facilitates viral replication in macrophages. The mechanism is that miR-92a directly targets RIG-I and reduces its expression, thereby attenuating VSV-triggered activation of TBK-binding kinase 1 and IRF3, both of which are crucial for initiating transcription of type-I IFN genes. Our results demonstrate for the first time the novel role of miR-92a in suppressing antiviral innate immunity., (© 2018 The Societies and John Wiley & Sons Australia, Ltd.)

Type I interferon (IFN-I) plays a critical role in the antiviral immune response. However, viruses have developed different strategies to suppress the production of IFN-I for its own escape and amplification. Therefore, promoting the production of IFN-I is an effective strategy against virus infection. Gastrodin (GTD), a phenolic glucoside extracted from Gastrodia elata Blume, has been reported to play a protective role in some central nervous system -related diseases and is beneficial for the recovery of diseases by inhibiting inflammation. However, the effect of GTD on virus infection is largely unknown. Here we found GTD treatment increased the survival rate of mice infected with vesicular stomatitis virus (VSV) or herpes simplex virus-1 (HSV-1). The production of IFN-I was increased in GTD-treated mice or macrophages compared to the control group, during virus infection. Furthermore, the activation of interferon regulatory factor 3 (IRF3) was promoted by GTD in macrophages upon VSV and HSV-1 infection. Our results demonstrated that GTD could inhibit the VSV and HSV-1 infection by promoting the production of IFN-I in macrophages and might provide an effective strategy against virus infection. [ABSTRACT FROM AUTHOR]