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PLoS One. 2009 Oct 27;4(10):e7582. doi: 10.1371/journal.pone.0007582.

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

Author information

1
Institut Pasteur, Unité de Défense Innée et Inflammation, Paris, France.

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.

PMID:
19859543
PMCID:
PMC2762520
DOI:
10.1371/journal.pone.0007582
[Indexed for MEDLINE]
Free PMC Article

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