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 journalArticle

44 Citations (Scopus)

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 (US)
Pages (from-to)3733-3745
Number of pages13
JournalJournal of Virology
Volume85
Issue number8
DOIs
StatePublished - Apr 1 2011

Fingerprint

Pestivirus Infections
Bovine Viral Diarrhea Viruses
Pestivirus
ubiquitin-protein ligase
Ubiquitin-Protein Ligases
interferons
Interferon Regulatory Factor-3
Interferons
Antiviral Agents
Bovine viral diarrhea virus
Viruses
viruses
Peptide Hydrolases
infection
Biological Phenomena
Vesicular Stomatitis
proteinases
proteins
Proteasome Endopeptidase Complex
Virus Replication

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

TRIM56 is a virus- and interferon-inducible E3 ubiquitin ligase that restricts pestivirus infection. / Wang, Jie; Liu, Baoming; Wang, Nan; Lee, Young Min; Liu, Chunming; Li, Kui.

In: Journal of Virology, Vol. 85, No. 8, 01.04.2011, p. 3733-3745.

Research output: Contribution to journalArticle

Wang, Jie ; Liu, Baoming ; Wang, Nan ; Lee, Young Min ; Liu, Chunming ; Li, Kui. / TRIM56 is a virus- and interferon-inducible E3 ubiquitin ligase that restricts pestivirus infection. In: Journal of Virology. 2011 ; Vol. 85, No. 8. pp. 3733-3745.
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