Overlapping and distinct molecular determinants dictating the antiviral activities of TRIM56 against flaviviruses and coronavirus

Baoming Liu, Nan L. Li, Jie Wang, Pei-Yong Shi, Tianyi Wang, Mark A. Miller, Kui Li

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The tripartite motif-containing (TRIM) proteins have emerged as a new class of host antiviral restriction factors, with several demonstrating roles in regulating innate antiviral responses. Of>70 known TRIMs, TRIM56 inhibits replication of bovine viral diarrhea virus, a ruminant pestivirus of the family Flaviviridae, but has no appreciable effect on vesicular stomatitis virus (VSV), a rhabdovirus. Yet the antiviral spectrum of TRIM56 remains undefined. In particular, how TRIM56 impacts human-pathogenic viruses is unknown. Also unclear are the molecular determinants governing the antiviral activities of TRIM56. Herein, we show that TRIM56 poses a barrier to infections by yellow fever virus (YFV), dengue virus serotype 2 (DENV2), and human coronavirus virus (HCoV) OC43 but not encephalomyocarditis virus (EMCV). Moreover, by engineering cell lines conditionally expressing various TRIM56 mutants, we demonstrated that TRIM56's antiflavivirus effects required both the E3 ligase activity that lies in the N-terminal RING domain and the integrity of its C-terminal portion, while the restriction of HCoV-OC43 relied upon the TRIM56 E3 ligase activity alone. Furthermore, TRIM56 was revealed to impair YFV and DENV2 propagation by suppressing intracellular viral RNA accumulation but to compromise HCoV-OC43 infection at a later step in the viral life cycle, suggesting that distinct TRIM56 domains accommodate differing antiviral mechanisms. Altogether, TRIM56 is a versatile antiviral host factor that confers resistance to YFV, DENV2, and HCoV-OC43 through overlapping and distinct molecular determinants.

Original languageEnglish (US)
Pages (from-to)13821-13835
Number of pages15
JournalJournal of Virology
Volume88
Issue number23
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

Flaviviridae
Flavivirus
Coronavirus
Coronavirinae
Human Coronavirus OC43
Yellow fever virus
Antiviral Agents
Dengue virus
viruses
Dengue Virus
Viruses
Ubiquitin-Protein Ligases
ligases
Encephalomyocarditis virus
Rhabdoviridae
Vesiculovirus
Pestivirus
Bovine viral diarrhea virus
Bovine Viral Diarrhea Viruses
Vesicular Stomatitis

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Overlapping and distinct molecular determinants dictating the antiviral activities of TRIM56 against flaviviruses and coronavirus. / Liu, Baoming; Li, Nan L.; Wang, Jie; Shi, Pei-Yong; Wang, Tianyi; Miller, Mark A.; Li, Kui.

In: Journal of Virology, Vol. 88, No. 23, 2014, p. 13821-13835.

Research output: Contribution to journalArticle

Liu, Baoming ; Li, Nan L. ; Wang, Jie ; Shi, Pei-Yong ; Wang, Tianyi ; Miller, Mark A. ; Li, Kui. / Overlapping and distinct molecular determinants dictating the antiviral activities of TRIM56 against flaviviruses and coronavirus. In: Journal of Virology. 2014 ; Vol. 88, No. 23. pp. 13821-13835.
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