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

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-beta) gene transcription. Another helicase protein, LGP2, lacks the CARD region and does not activate IFN-beta 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 IKKepsilon) 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.

journal_name

J Virol

journal_title

Journal of virology

authors

Komuro A,Horvath CM

doi

10.1128/JVI.01325-06

subject

Has Abstract

pub_date

2006-12-01 00:00:00

pages

12332-42

issue

24

eissn

0022-538X

issn

1098-5514

pii

JVI.01325-06

journal_volume

80

pub_type

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