Inducible Rubicon facilitates viral replication by antagonizing interferon production

Yushun Wan, Wei Cao, Tao Han, Sheng Ren, Jian Feng, Tie Long Chen, Jun Wang, Ruth Broering, Mengji Lu, Ying Zhu

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

The RUN domain Beclin-1-interacting cysteine-rich-containing (Rubicon) protein is involved in the maturation step of autophagy and the endocytic pathway as a Beclin-1-binding partner, but little is known regarding the role of Rubicon during viral infection. Here, we performed functional studies of the identified target in interferon (IFN) signaling pathways associated with Rubicon to elucidate the mechanisms of viral resistance to IFN. The Rubicon protein levels were elevated in peripheral blood mononuclear cells, sera and liver tissues from patients with hepatitis B virus (HBV) infection relative to those in healthy individuals. Assays of the overexpression and knockdown of Rubicon showed that Rubicon significantly promoted HBV replication. In addition, Rubicon knockdown resulted in the inhibition of enterovirus 71, influenza A virus and vesicular stomatitis virus. The expression o0f Rubicon led to the suppression of virus-induced type-I interferon (IFN-α and IFN-β) and type-III interferon (IFN-Î" 1). Translocation of activated IRF3 and IRF7 from the cytoplasm to the nucleus was involved in this process, and the NF-ΰ B essential modulator (NEMO), a key factor in the IFN pathway, was the target with which Rubicon interacted. Our results reveal a previously unrecognized function of Rubicon as a virus-induced protein that binds to NEMO, leading to the inhibition of type-I interferon production. Rubicon thus functions as an important negative regulator of the innate immune response, enhances viral replication and may play a role in viral immune evasion.

Original languageEnglish (US)
Pages (from-to)607-620
Number of pages14
JournalCellular and Molecular Immunology
Volume14
Issue number7
DOIs
StatePublished - Jul 1 2017
Externally publishedYes

Keywords

  • Host response
  • Rubicon
  • immune evasion
  • interferon
  • viral infection!

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