RNA- and virus-independent inhibition of antiviral signaling by RNA helicase LGP2

Akihiko Komuro, Curt M. Horvath*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

213 Scopus citations

Abstract

Antiviral innate immune responses can be triggered by accumulation of intracellular nucleic acids resulting from virus infections. Double-stranded RNA (dsRNA) can be detected by the cytoplasmic RNA helicase proteins RIG-I and MDA5, two proteins that share sequence similarities within a caspase recruitment domain (CARD) and a DExD/H box RNA helicase domain. These proteins are considered dsRNA sensors and are thought to transmit the signal to the mitochondrial adapter, IPS-1 (also known as MAVS, VISA, or CARDIF) via CARD interactions. IPS-1 coordinates the activity of protein kinases that activate transcription factors needed to induce beta interferon (IFN-β) gene transcription. Another helicase protein, LGP2, lacks the CARD region and does not activate IFN-β gene expression. LGP2 mRNA is induced by interferon, dsRNA treatments, or Sendai virus infection and acts as a feedback inhibitor for antiviral signaling. Results indicate that LGP2 can inhibit antiviral signaling independently of dsRNA or virus infection intermediates by engaging in a protein complex with IPS-1. Experiments suggest that LGP2 can compete with the kinase IKKi (also known as IKKε) for a common interaction site on IPS-1. These results provide the first demonstration of protein interaction as an element of negative-feedback regulation of intracellular antiviral signaling by LGP2.

Original languageEnglish (US)
Pages (from-to)12332-12342
Number of pages11
JournalJournal of virology
Volume80
Issue number24
DOIs
StatePublished - Dec 2006

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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