RNA- and virus-independent inhibition of antiviral signaling by RNA helicase LGP2.
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.
Komuro
Akihiko
A
Pancoe-ENH Research Pavilion, Northwestern University, 2200 Campus Drive, Evanston, IL 60208, USA.
Horvath
Curt M
CM
D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D017931:DNA Primers; D004266:DNA Virus Infections / Q000276:immunology*; D025461:Feedback, Physiological / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology*; D006801:Humans; D047468:Immunoprecipitation; D008156:Luciferases; D020365:RNA Helicases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*
D048868:Adaptor Proteins, Signal Transducing; D017931:DNA Primers; C505371:MAVS protein, human; D012333:RNA, Messenger; D008156:Luciferases; D020365:RNA Helicases