Study of Human RIG-I Polymorphisms Identifies Two Variants with an Opposite Impact on the Antiviral Immune Response


Journal article


Julien Pothlichet, Anne Burtey, A. Kubarenko, G. Caignard, B. Solhonne, F. Tangy, M. Ben-ali, L. Quintana-Murci, A. Heinzmann, J. Chiche, P. Vidalain, A. Weber, M. Chignard, M. Si-Tahar
PLoS ONE, 2009

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APA   Click to copy
Pothlichet, J., Burtey, A., Kubarenko, A., Caignard, G., Solhonne, B., Tangy, F., … Si-Tahar, M. (2009). Study of Human RIG-I Polymorphisms Identifies Two Variants with an Opposite Impact on the Antiviral Immune Response. PLoS ONE.


Chicago/Turabian   Click to copy
Pothlichet, Julien, Anne Burtey, A. Kubarenko, G. Caignard, B. Solhonne, F. Tangy, M. Ben-ali, et al. “Study of Human RIG-I Polymorphisms Identifies Two Variants with an Opposite Impact on the Antiviral Immune Response.” PLoS ONE (2009).


MLA   Click to copy
Pothlichet, Julien, et al. “Study of Human RIG-I Polymorphisms Identifies Two Variants with an Opposite Impact on the Antiviral Immune Response.” PLoS ONE, 2009.


BibTeX   Click to copy

@article{julien2009a,
  title = {Study of Human RIG-I Polymorphisms Identifies Two Variants with an Opposite Impact on the Antiviral Immune Response},
  year = {2009},
  journal = {PLoS ONE},
  author = {Pothlichet, Julien and Burtey, Anne and Kubarenko, A. and Caignard, G. and Solhonne, B. and Tangy, F. and Ben-ali, M. and Quintana-Murci, L. and Heinzmann, A. and Chiche, J. and Vidalain, P. and Weber, A. and Chignard, M. and Si-Tahar, M.}
}

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 (P229fs) that generates a truncated, constitutively active receptor and (ii) a serine to isoleucine mutation (S183I), 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 P229fs and S183I 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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