TRIM56 is a virus- and interferon-inducible E3 ubiquitin ligase that restricts pestivirus infection

Jie Wang, Baoming Liu, Nan Wang, Young Min Lee, Chunming Liu, Kui Li

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

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.

Original languageEnglish
Pages (from-to)3733-3745
Number of pages13
JournalJournal of Virology
Volume85
Issue number8
DOIs
StatePublished - Apr 2011

Bibliographical note

Funding Information:
Funding: this work was funded by Pfiz‑ er Inc. Medical writing support, under the guidance of the authors, was provid‑ ed by Karen Irving, PhD, CMC Con‑ nect, McCann Health Medical Commu‑ nications and Kirsteen Munn, PhD, on behalf of CMC Connect, and was fund‑ ed by Pfizer Inc, New York, NY, USA in accordance with Good Publication Practice (GPP3) guidelines (Ann Intern Med 2015; 163: 461-4). Pfizer employ‑ ees reviewed and provided feedback on the manuscript content for the authors’ consideration. The authors retained full editorial control of the content.

Funding Information:
this work was funded by Pfiz? er Inc. Medical writing support, under the guidance of the authors, was provid? ed by Karen Irving, PhD, CMC Con? nect, McCann Health Medical Commu? nications and Kirsteen Munn, PhD, on behalf of CMC Connect, and was fund? ed by Pfizer Inc, New York, NY, USA in accordance with Good Publication Practice (GPP3) guidelines (Ann Intern Med 2015; 163: 461-4). Pfizer employ? ees reviewed and provided feedback on the manuscript content for the authors? consideration. The authors retained full editorial control of the content.

Funding Information:
received grant/research support from Bristol‑Myers Squibb, and consult‑ ing fees from AbbVie, Bristol‑Myers Squibb, Galapagos, Gilead, GSK, Lilly, Pfizer Inc, Roche and UCB. Y. Tanaka has received speaker fees and/or honoraria from AbbVie, Asahi Kasei, Astellas, Bristol‑Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lil‑ ly, Gilead, GSK, Janssen, Mitsubishi Tanabe, Novartis, Pfizer Inc, Sanofi and YL Biologics; and has received grant/ research support from AbbVie, Chu‑ gai, Daiichi Sankyo, Eisai, Mitsubishi Tanabe, Takeda and UCB. E.B. Lee has received consulting fees from Pfizer Inc, and grant/research sup‑ port from GC Pharma and Handok Inc. J. Wollenhaupt has received consulting fees and speaker fees from Pfizer Inc. V.F. Azevedo has received grant/ research support from AbbVie, GSK, Janssen, Lilly, Pfizer Inc and UCB; and has received speaker fees from AbbVie, Janssen, Lilly, Novartis and Pfizer Inc. J.R. Curtis has received consulting fees and grant/research support from GSK and Pfizer Inc, and was previously a member of the Centers for Disease Control and Prevention Advisory Com‑ mittee on Immunization Practices Her‑ pes Zoster working group. A. Al Enizi has declared no competing interests.

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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