Ubiquitin-conjugating enzyme UBE2J1 negatively modulates interferon pathway and promotes RNA virus infection
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RESEARCH
Open Access
Ubiquitin-conjugating enzyme UBE2J1 negatively modulates interferon pathway and promotes RNA virus infection Tingting Feng1, Lei Deng1, Xiaochuan Lu1, Wen Pan1, Qihan Wu2* and Jianfeng Dai1,2*
Abstract Background: Viral infection activates innate immune pathways and interferons (IFNs) play a pivotal role in the outcome of a viral infection. Ubiquitin modifications of host and viral proteins significantly influence the progress of virus infection. Ubiquitin-conjugating enzyme E2s (UBE2) have the capacity to determine ubiquitin chain topology and emerge as key mediators of chain assembly. Methods: In this study, we screened the functions of 34 E2 genes using an RNAi library during Dengue virus (DENV) infection. RNAi and gene overexpression approaches were used to study the gene function in viral infection and interferon signaling. Results: We found that silencing UBE2J1 significantly impaired DENV infection, while overexpression of UBE2J1 enhanced DENV infection. Further studies suggested that type I IFN expression was significantly increased in UBE2J1 silenced cells and decreased in UBE2J1 overexpressed cells. Reporter assay suggested that overexpression of UBE2J1 dramatically suppressed RIG-I directed IFNβ promoter activation. Finally, we have confirmed that UBE2J1 can facilitate the ubiquitination and degradation of transcription factor IFN regulatory factor 3 (IRF3). Conclusion: These results suggest that UBE2 family member UBE2J1 can negatively regulate type I IFN expression, thereby promote RNA virus infection. Keywords: UBE2J1, Dengue virus, Interferons, IRF3, K48 ubiquitination
Background Dengue virus (DENV), transmitted by Aedes aegypti and Aedes albopicuts, causes an emerging tropical disease that arouses increasing public concern in recent years [1, 2]. Up to 1.5 million infected individuals present with clinical symptoms and ~ 500,000 infections progress to the life-threatening dengue hemorrhagic fever and dengue shock syndrome. No specific treatment for dengue infection is available at the moment. Viral infection activates innate sensing pathways. Interferons (IFNs) play a pivotal role in the outcome of a viral infection, and regulate both innate and adaptive * Correspondence: [email protected]; [email protected] 2 Key Laboratory of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan University, Shanghai Institute of Planned Parenthood Research, Shanghai 200032, People’s Republic of China 1 Institute of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection and Immunity, Soochow University, 199 Ren-ai Road, Suzhou 215123, People’s Republic of China
antiviral responses [3]. IFN-α/β regulates the synthesis of antiviral proteins and immunoregulatory factors through the JAK/STAT signaling pathway [4, 5]. A lot of host and viral proteins can regulate the type I interferon pathway thereby significantly influence the progress of virus infection. Ubiquitin modifications of proteins within the signaling cascades induce type I interferon expression, and in contrast, s
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