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Published on: January 1, 2018
RIG-I and dsRNA-induced IFNbeta activation
Stéphane Hausmann1, Jean-Baptiste Marq, Caroline Tapparel
1Department of Microbiology and Molecular Medicine, University of Geneva Medical School, Geneva, Switzerland.
Abstract:
Except for viruses that initiate RNA synthesis with a protein primer (e.g., picornaviruses), most RNA viruses initiate RNA synthesis with an NTP, and at least some of their viral (ppp)RNAs remain unblocked during the infection. Consistent with this, most viruses require RIG-I to mount an innate immune response, whereas picornaviruses require mda-5. We have examined a SeV infection whose ability to induce interferon depends on the generation of capped dsRNA (without free 5' tri-phosphate ends), and found that this infection as well requires RIG-I and not mda-5. We also provide evidence that RIG-I interacts with poly-I/C in vivo, and that heteropolymeric dsRNA and poly-I/C interact directly with RIG-I in vitro, but in different ways; i.e., poly-I/C has the unique ability to stimulate the helicase ATPase of RIG-I variants which lack the C-terminal regulatory domain.
Insights
Most RNA viruses trigger innate immunity via RIG-I, but picornaviruses use mda-5. SeV infection, like other RNA viruses, requires RIG-I, not mda-5, for interferon induction.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Most RNA viruses initiate RNA synthesis with NTPs, leaving some viral RNAs unblocked.
- Innate immune responses to RNA viruses typically involve RIG-I, except for picornaviruses which utilize mda-5.
Purpose of the Study:
- To investigate the innate immune response triggered by Sendai virus (SeV) infection.
- To determine the role of RIG-I and mda-5 in SeV-induced interferon production.
Main Methods:
- Examined SeV infection in the context of interferon induction.
- Assessed the interaction of RIG-I with dsRNA (poly-I/C) in vitro and in vivo.
Main Results:
- SeV infection induces interferon, dependent on capped dsRNA without free 5' tri-phosphate ends.
- This SeV-induced interferon response requires RIG-I, not mda-5.
- RIG-I interacts with poly-I/C in vivo and in vitro, with poly-I/C uniquely stimulating RIG-I ATPase activity in variants lacking the C-terminal domain.
Conclusions:
- Sendai virus infection elicits an innate immune response mediated by RIG-I.
- RIG-I recognizes specific dsRNA structures, with distinct interactions observed for poly-I/C compared to other dsRNAs.
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