DOI: 10.1128/jvi.01325-06. RNA- and Virus-Independent Inhibition of Antiviral Signaling by RNA Helicase LGP2

RNA- and Virus-Independent Inhibition of Antiviral Signaling by RNA Helicase LGP2

10.1128/jvi.01325-06

Crossref journal-article

American Society for Microbiology

Journal of Virology (235)

Abstract

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.

Authors 2

Akihiko Komuro (first)
Curt M. Horvath (additional)

References 31 Referenced 240

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Dates

Type	When
Created	18 years, 9 months ago (Nov. 27, 2006, 6:43 p.m.)
Deposited	3 years, 5 months ago (March 5, 2022, 5:34 a.m.)
Indexed	1 month ago (July 28, 2025, 5:36 p.m.)
Issued	18 years, 8 months ago (Dec. 15, 2006)
Published	18 years, 8 months ago (Dec. 15, 2006)
Published Print	18 years, 8 months ago (Dec. 15, 2006)

Funders 0

None

BibTeX

@article{Komuro_2006, title={RNA- and Virus-Independent Inhibition of Antiviral Signaling by RNA Helicase LGP2}, volume={80}, ISSN={1098-5514}, url={http://dx.doi.org/10.1128/jvi.01325-06}, DOI={10.1128/jvi.01325-06}, number={24}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Komuro, Akihiko and Horvath, Curt M.}, year={2006}, month=dec, pages={12332–12342} }

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  "abstract": "<jats:title>ABSTRACT</jats:title>\n          <jats:p>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-\u03b2) gene transcription. Another helicase protein, LGP2, lacks the CARD region and does not activate IFN-\u03b2 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 IKK\u03b5) 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.</jats:p>",
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