title: TRIM56 is a virus- and interferon-inducible E3 ubiquitin ligase that restricts pestivirus infection.
abstract: The tripartite motif (TRIM) protein family comprises more than 60 members that have diverse functions in various biological processes. Although a small number of TRIM proteins have been shown to regulate innate immunity, much remains to be learned about the functions of the majority of the TRIM proteins. Here we identify TRIM56 as a cellular protein associated with the N-terminal protease (N(pro)) of bovine viral diarrhea virus (BVDV), a pestiviral interferon antagonist which degrades interferon regulatory factor 3 (IRF3) through the proteasome. We found that TRIM56 was constitutively expressed in most tissues, and its abundance was further upregulated moderately by interferon or virus. The manipulation of TRIM56 abundance did not affect the protein turnover of N(pro) and IRF3. Rather, ectopic expression of TRIM56 substantially impaired, while knockdown of TRIM56 expression greatly enhanced, BVDV replication in cell culture. The antiviral activity of TRIM56 depended on its E3 ubiquitin ligase activity as well as the integrity of its C-terminal region but was not attributed to a general augmentation of the interferon antiviral response. Overexpression of TRIM56 did not inhibit the replication of vesicular stomatitis virus or hepatitis C virus, a virus closely related to BVDV. Together, our data demonstrate that TRIM56 is a novel antiviral host factor that restricts pestivirus infection.
authors.affiliation: Department of Microbiology, University of Tennessee Health Science Center, 858 Madison Avenue, Memphis, TN 38163, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.forename: Baoming
authors.initials: B
authors.lastname: Liu
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.forename: Young-Min
authors.initials: YM
authors.lastname: Lee
authors.forename: Chunming
authors.initials: C
authors.lastname: Liu
authors.forename: Kui
authors.initials: K
authors.lastname: Li
mesh_terms: D000818:Animals; D002460:Cell Line; D001908:Diarrhea Viruses, Bovine Viral / Q000276:immunology; D016174:Hepacivirus / Q000276:immunology; D006801:Humans; D007372:Interferons / Q000276:immunology; D018182:Pestivirus Infections / Q000276:immunology*; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000276:immunology*; D018116:Vesiculovirus / Q000276:immunology
chemical_list: D000070584:Tripartite Motif Proteins; D007372:Interferons; C554560:TRIM56 protein, human; D044767:Ubiquitin-Protein Ligases