Inducible Rubicon facilitates viral replication by antagonizing interferon production  

作　　者：Yushun Wan Wei Cao Tao Han Sheng Ren Jian Feng TieLong Chen Jun Wang Ruth Broering Mengji Lu Ying Zhu 

机构地区：[1]State Key Laboratory of Virology and College of Life Sciences,Wuhan University,Wuhan 430072,China [2]Department of Infectious Diseases,Zhongnan Hospital of Wuhan University,Wuhan 430072,China [3]Medical Faculty,Department of Gastroenterology and Hepatology,University of Duisburg-Essen,Essen 45127,Germany [4]Institute of Virology,University of Duisburg-Essen,Essen 45127,Germany

出　　处：《Cellular & Molecular Immunology》2017年第7期607-620,共14页中国免疫学杂志（英文版）

基　　金：the supporting of special funding for the PhD students of Wuhan University short-term study abroad;supported by research grants from the Major State Basic Research Development Program of China(2013CB911102);the National Natural Science Foundation of China(81461130019,81271821 and 31570870).

摘　　要：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-αand 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.

关 键 词：host response immune evasion INTERFERON RUBICON viral infection 

分 类 号：R51[医药卫生—内科学]