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Public Library of Science, PLoS ONE, 10(4), p. e7582, 2009

DOI: 10.1371/journal.pone.0007582

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Study of human RIG-I polymorphisms identifies two variants with an opposite impact on the antiviral immune response.

Journal article published in 2009 by Julien Pothlichet, Anne Burtey, Andriy V. Kubarenko, Gregory Caignard, Brigitte Solhonne, Frédéric Tangy, Meriem Ben-Ali, Lluis Quintana-Murci, Andrea Heinzmann, Jean-Daniel Chiche ORCID, Pierre-Olivier Vidalain, Alexander N. R. Weber, Michel Chignard, Mustapha Si-Tahar ORCID
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

BACKGROUND: RIG-I is a pivotal receptor that detects numerous RNA and DNA viruses. Thus, its defectiveness may strongly impair the host antiviral immunity. Remarkably, very little information is available on RIG-I single-nucleotide polymorphisms (SNPs) presenting a functional impact on the host response. METHODOLOGY/PRINCIPAL FINDINGS: Here, we studied all non-synonymous SNPs of RIG-I using biochemical and structural modeling approaches. We identified two important variants: (i) a frameshift mutation (P(229)fs) that generates a truncated, constitutively active receptor and (ii) a serine to isoleucine mutation (S(183)I), which drastically inhibits antiviral signaling and exerts a down-regulatory effect, due to unintended stable complexes of RIG-I with itself and with MAVS, a key downstream adapter protein. CONCLUSIONS/SIGNIFICANCE: Hence, this study characterized P(229)fs and S(183)I SNPs as major functional RIG-I variants and potential genetic determinants of viral susceptibility. This work also demonstrated that serine 183 is a residue that critically regulates RIG-I-induced antiviral signaling.