The TAR-RNA binding protein is required for immunoresponses triggered by Cardiovirus infection.

Abstract

LGP2 and MDA5 cooperate to detect viral RNA in the cytoplasm of Picornavirus-infected cells and activate innate immune responses. To further define regulatory components of RNA recognition by LGP2/MDA5, a yeast two-hybrid screen was used to identify LGP2-interacting proteins. The screening has identified the TAR-RNA binding protein (TRBP), which is known to be an essential factor for RNA interference (RNAi). Immuno-precipitation experiments demonstrated that TRBP interacted specifically with LGP2 but not with related RIG-I-like receptors, RIG-I or MDA5. siRNA knockdown experiments indicate that TRBP is important for Cardiovirus-triggered interferon responses, but TRBP is not involved in Sendai virus-triggered interferon response that is mediated mainly by RIG-I. To support functional interaction with LGP2, overexpressed TRBP increased Cardiovirus-triggered interferon promoter activity only when LGP2 and MDA5 are co-expressed but not MDA5 alone. Together, our findings illustrate a possible connection between an RNAi-regulatory factor and antiviral RNA recognition that is specifically required for a branch of the virus induced innate immune response.

• Authors: Akihiko Komuro, Yuya Homma, Takaharu Negoro, Glen N Barber, Curt M Horvath
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 480 Issue 2 Pg. 187-193 (11 11 2016) ISSN: 1090-2104 [Electronic] United States
• PMID: 27743889 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• RNA, Small Interfering
• RNA-Binding Proteins
• Receptors, Immunologic
• trans-activation responsive RNA-binding protein
• Interferon-beta
• DHX58 protein, human
• DDX58 protein, human
• IFIH1 protein, human
• DEAD Box Protein 58
• Interferon-Induced Helicase, IFIH1
• RNA Helicases

Topics

• Animals
• Cardiovirus (pathogenicity)
• Cardiovirus Infections (immunology, metabolism)
• Chlorocebus aethiops
• DEAD Box Protein 58 (genetics, metabolism)
• HEK293 Cells
• Host-Pathogen Interactions
• Humans
• Interferon-Induced Helicase, IFIH1 (genetics)
• Interferon-beta (genetics)
• Mice
• Promoter Regions, Genetic
• RNA Helicases (genetics, metabolism)
• RNA, Small Interfering
• RNA-Binding Proteins (genetics, metabolism)
• Receptors, Immunologic
• Sendai virus (pathogenicity)
• Vero Cells