The C-terminal tail of TRIM56 dictates antiviral restriction of influenza A and B viruses by impeding viral RNA synthesis

Baoming Liu, Nan L. Li, Yang Shen, Xiaoyong Bao, Thomas Fabrizio, Husni Elbahesh, Richard J. Webby, Kui Li

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Accumulating data suggest that tripartite-motif-containing (TRIM) proteins participate in host responses to viral infections, either by acting as direct antiviral restriction factors or through regulating innate immune signaling of the host. Of > 70 TRIMs, TRIM56 is a restriction factor of several positive-strand RNA viruses, including three members of the family Flaviviridae (yellow fever virus, dengue virus, and bovine viral diarrhea virus) and a human coronavirus (OC43), and this ability invariably depends upon the E3 ligase activity of TRIM56. However, the impact of TRIM56 on negative-strand RNA viruses remains unclear. Here, we show that TRIM56 puts a check on replication of influenza A and B viruses in cell culture but does not inhibit Sendai virus or human metapneumovirus, two paramyxoviruses. Interestingly, the anti-influenza virus activity was independent of the E3 ligase activity, B-box, or coiled-coil domain. Rather, deletion of a 63-residue-long C-terminal-tail portion of TRIM56 abrogated the antiviral function. Moreover, expression of this short C-terminal segment curtailed the replication of influenza viruses as effectively as that of full-length TRIM56. Mechanistically, TRIM56 was found to specifically impede intracellular influenza virus RNA synthesis. Together, these data reveal a novel antiviral activity of TRIM56 against influenza A and B viruses and provide insights into the mechanism by which TRIM56 restricts these medically important orthomyxoviruses.

Original languageEnglish (US)
Pages (from-to)4369-4382
Number of pages14
JournalJournal of Virology
Volume90
Issue number9
DOIs
StatePublished - May 1 2016

Fingerprint

Influenza B virus
Influenza A virus
Viral RNA
Orthomyxoviridae
Antiviral Agents
tail
RNA
Ubiquitin-Protein Ligases
synthesis
RNA Viruses
ligases
Human coronavirus OC43
Human Coronavirus OC43
Human metapneumovirus
Yellow fever virus
Flaviviridae
Metapneumovirus
Sendai virus
Bovine Viral Diarrhea Viruses
Respirovirus

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

The C-terminal tail of TRIM56 dictates antiviral restriction of influenza A and B viruses by impeding viral RNA synthesis. / Liu, Baoming; Li, Nan L.; Shen, Yang; Bao, Xiaoyong; Fabrizio, Thomas; Elbahesh, Husni; Webby, Richard J.; Li, Kui.

In: Journal of Virology, Vol. 90, No. 9, 01.05.2016, p. 4369-4382.

Research output: Contribution to journalArticle

Liu, Baoming ; Li, Nan L. ; Shen, Yang ; Bao, Xiaoyong ; Fabrizio, Thomas ; Elbahesh, Husni ; Webby, Richard J. ; Li, Kui. / The C-terminal tail of TRIM56 dictates antiviral restriction of influenza A and B viruses by impeding viral RNA synthesis. In: Journal of Virology. 2016 ; Vol. 90, No. 9. pp. 4369-4382.
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