Interferon-inducible protein IFI35 negatively regulates RIG-I antiviral signaling and supports vesicular stomatitis virus replication

Anshuman Das, Phat X. Dinh, Debasis Panda, Asit K Pattnaik

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

In a genome-wide small interferingRNA(siRNA) screen, we recently identified the interferon (IFN)-inducible protein 35 (IFI35; also known as IFP35) as a factor required for vesicular stomatitis virus (VSV) infection. Studies reported here were conducted to further understand the role and requirement of IFI35 in VSV infection. Consistent with the siRNA screening data, we found that depletion of IFI35 led to reduced VSV replication at the level of viral gene expression. Although no direct interaction of IFI35 with the viral replication machinery was observed, we found that IFI35 negatively regulated the host innate immune response and rescued poly(I·C)-induced inhibition of VSV replication. Promoter-driven reporter gene assays demonstrated that IFI35 overexpression suppressed the activation of IFN-β and ISG56 promoters, whereas its depletion had the opposite effect. Further investigation revealed that IFI35 specifically interacted with retinoic acid-inducible gene I (RIG-I) and negatively regulated its activation through mechanisms that included (i) suppression of dephosphorylation (activation) of RIG-I and (ii) proteasome-mediated degradation of RIG-I via K48-linked ubiquitination. Overall, the results presented here suggest a novel role for IFI35 in negative regulation of RIG-I-mediated antiviral signaling, which will have implications for diseases associated with excessive immune signaling.

Original languageEnglish (US)
Pages (from-to)3103-3113
Number of pages11
JournalJournal of virology
Volume88
Issue number6
DOIs
StatePublished - Jan 1 2014

Fingerprint

Vesiculovirus
Vesicular Stomatitis
retinoic acid
interferons
Virus Replication
virus replication
Tretinoin
Interferons
Antiviral Agents
Virus Diseases
Genes
Proteins
genes
proteins
promoter regions
polyinosinic-polycytidylic acid
Viral Genes
dephosphorylation
Ubiquitination
proteasome endopeptidase complex

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Interferon-inducible protein IFI35 negatively regulates RIG-I antiviral signaling and supports vesicular stomatitis virus replication. / Das, Anshuman; Dinh, Phat X.; Panda, Debasis; Pattnaik, Asit K.

In: Journal of virology, Vol. 88, No. 6, 01.01.2014, p. 3103-3113.

Research output: Contribution to journalArticle

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