title: Inducible Rubicon facilitates viral replication by antagonizing interferon production.
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-λ1). Translocation of activated IRF3 and IRF7 from the cytoplasm to the nucleus was involved in this process, and the NF-κB 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.
authors.affiliation: State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Yushun
authors.initials: Y
authors.lastname: Wan
authors.affiliation: State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Han
authors.affiliation: State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Ren
authors.affiliation: State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Feng
authors.affiliation: Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Wuhan 430072, China.
authors.forename: TieLong
authors.initials: T
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Medical Faculty, Department of Gastroenterology and Hepatology, University of Duisburg-Essen, Essen 45127, Germany.
authors.forename: Ruth
authors.initials: R
authors.lastname: Broering
authors.affiliation: Institute of Virology, University of Duisburg-Essen, Essen 45127, Germany.
authors.forename: Mengji
authors.initials: M
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhu
mesh_terms: D000071183:Autophagy-Related Proteins; D045744:Cell Line, Tumor; D006515:Hepatitis B virus / Q000502:physiology; D019694:Hepatitis B, Chronic / Q000378:metabolism / Q000821:virology; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D051550:I-kappa B Kinase; D007372:Interferons / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008954:Models, Biological; D010766:Phosphorylation; D011485:Protein Binding; D054875:Ubiquitination; D014779:Virus Replication
chemical_list: D000071183:Autophagy-Related Proteins; C491731:IKBKG protein, human; D047908:Intracellular Signaling Peptides and Proteins; C552537:RUBCN protein, human; D007372:Interferons; D051550:I-kappa B Kinase