title: Innate immune evasion by hepatitis B virus-mediated downregulation of TRIF.
abstract: Hepatocytes are the target host cells during hepatitis B virus (HBV) infection. Recent studies indicate that the innate immune response of hepatocytes plays an important role in inhibiting HBV replication. TIR-domain-containing adaptor inducing interferon-beta (TRIF) is a key component in innate immune signaling pathways. In this study, we found that the TRIF protein was downregulated in human hepatoma cell lines and liver tissue samples harboring HBV. Hepatitis B virus X protein (HBX) reduced TRIF protein expression in a dose-dependent manner via the proteasomal pathway. HBX appeared to not directly interact with TRIF as these proteins failed to co-immunoprecipitate when overexpressed in hepatoma cells. TRIF upregulation in hepatoma cell lines dramatically inhibited HBV transcription and expression of its viral proteins. Cellular apoptosis induced by TRIF was also confirmed in hepatoma cell lines. Taken together, these findings reveal a new mechanism for HBV evasion of the cellular innate immunity by HBX-mediated degradation of TRIF protein in hepatocytes.
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Qingchun Road 79, Hangzhou, Zhejiang 310003, China; Key Laboratory of Combined Multi-organ Transplantation of Ministry of Public Health, Qingchun Road 79, Hangzhou, Zhejiang 310003, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Hong
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Qingchun Road 79, Hangzhou, Zhejiang 310003, China; Key Laboratory of Combined Multi-organ Transplantation of Ministry of Public Health, Qingchun Road 79, Hangzhou, Zhejiang 310003, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Qingchun Road 79, Hangzhou, Zhejiang 310003, China; Key Laboratory of Combined Multi-organ Transplantation of Ministry of Public Health, Qingchun Road 79, Hangzhou, Zhejiang 310003, China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Xie
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Qingchun Road 79, Hangzhou, Zhejiang 310003, China; Key Laboratory of Combined Multi-organ Transplantation of Ministry of Public Health, Qingchun Road 79, Hangzhou, Zhejiang 310003, China. Electronic address: shusenzheng@zju.edu.cn.
authors.forename: Shusen
authors.initials: S
authors.lastname: Zheng
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000502:physiology*; D001483:Base Sequence; D017931:DNA Primers; D004261:DNA Replication; D004279:DNA, Viral / Q000096:biosynthesis; D015536:Down-Regulation / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000235:genetics / Q000502:physiology*; D006801:Humans; D057131:Immune Evasion / Q000502:physiology*; D007113:Immunity, Innate; D060888:Real-Time Polymerase Chain Reaction; D015534:Trans-Activators / Q000502:physiology; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D017931:DNA Primers; D004279:DNA, Viral; C470409:TICAM1 protein, human; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein
keywords: Apoptosis; Hepatitis B virus; Innate immunity; TRIF; Virus replication