PloS one, 2009-10, Vol.4 (10), p.e7582-e7582
2009
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- Autor(en) / Beteiligte
- Titel
- Study of human RIG-I polymorphisms identifies two variants with an opposite impact on the antiviral immune response
- Ist Teil von
- PloS one, 2009-10, Vol.4 (10), p.e7582-e7582
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2009
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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. 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. 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0007582Titel-ID: cdi_plos_journals_1292581251
- Format
- –
- Schlagworte
- Adapter proteins, Adapters, adaptor proteins, Amino acids, Analysis, Antiviral agents, Antiviral Agents - chemistry, Apoptosis, B cells, Cell Line, Cytokines, DEAD Box Protein 58, DEAD-box RNA Helicases - genetics, Deoxyribonucleic acid, Dimerization, Disease susceptibility, DNA, DNA viruses, Frameshift mutation, Genetic aspects, Genetic Variation, Humans, Immune response, Immune System, Immunity, Immunity, Innate, Immunology/Genetics of the Immune System, Immunology/Immune Response, Immunology/Innate Immunity, Infectious Diseases/Viral Infections, Inflammation, Isoleucine, Kinases, Life Sciences, Microbiology and Parasitology, Models, Genetic, Models, Molecular, Mutagenesis, Mutation, Mutation, Missense, Phenotype, Polymorphism, Genetic, Polymorphism, Single Nucleotide, Receptors, Immunologic, Ribonucleic acid, RNA, RNA viruses, Serine, Signal Transduction, Signaling, Single nucleotide polymorphisms, Single-nucleotide polymorphism, Viral infections, Virology, Viruses