2. Academic Validation
  3. Ubiquitin-conjugating enzyme UBE2J1 negatively modulates interferon pathway and promotes RNA virus infection

Ubiquitin-conjugating enzyme UBE2J1 negatively modulates interferon pathway and promotes RNA virus infection

  • Virol J. 2018 Aug 29;15(1):132. doi: 10.1186/s12985-018-1040-5.
Tingting Feng 1,  Lei Deng 1,  Xiaochuan Lu 1,  Wen Pan 1,  Qihan Wu 2,  Jianfeng Dai 3 4
Affiliations

Affiliations

  • 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.
  • 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. [email protected].
  • 3 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. [email protected].
  • 4 Key Laboratory of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan University, Shanghai Institute of Planned Parenthood Research, Shanghai, 200032, People's Republic of China. [email protected].
PMID: 30157886 DOI: 10.1186/s12985-018-1040-5
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

Dengue virus; IRF3; Interferons; K48 ubiquitination; UBE2J1.

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