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

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.
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Submitted on : Thursday, February 11, 2010 - 10:54:25 AM
Last modification on : Thursday, August 27, 2020 - 3:10:05 PM
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Julien Pothlichet, Anne Burtey, Andriy V. Kubarenko, Gregory Caignard, Brigitte Solhonne, et al.. Study of human RIG-I polymorphisms identifies two variants with an opposite impact on the antiviral immune response.. PLoS ONE, Public Library of Science, 2009, 4 (10), pp.e7582. ⟨10.1371/journal.pone.0007582⟩. ⟨pasteur-00455204⟩

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