title: Alteration of Antiviral Signalling by Single Nucleotide Polymorphisms (SNPs) of Mitochondrial Antiviral Signalling Protein (MAVS).
abstract: Genetic variation is associated with diseases. As a type of genetic variation occurring with certain regularity and frequency, the single nucleotide polymorphism (SNP) is attracting more and more attention because of its great value for research and real-life application. Mitochondrial antiviral signalling protein (MAVS) acts as a common adaptor molecule for retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), which can recognize foreign RNA, including viral RNA, leading to the induction of type I interferons (IFNs). Therefore, MAVS is thought to be a crucial molecule in antiviral innate immunity. We speculated that genetic variation of MAVS may result in susceptibility to infectious diseases. To assess the risk of viral infection based on MAVS variation, we tested the effects of twelve non-synonymous MAVS coding-region SNPs from the National Center for Biotechnology Information (NCBI) database that result in amino acid substitutions. We found that five of these SNPs exhibited functional alterations. Additionally, four resulted in an inhibitory immune response, and one had the opposite effect. In total, 1,032 human genomic samples obtained from a mass examination were genotyped at these five SNPs. However, no homozygous or heterozygous variation was detected. We hypothesized that these five SNPs are not present in the Japanese population and that such MAVS variations may result in serious immune diseases.
authors.affiliation: Department of Vascular Biology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Fei
authors.initials: F
authors.lastname: Xing
authors.affiliation: Department of Vascular Biology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Tomoh
authors.initials: T
authors.lastname: Matsumiya
authors.affiliation: Department of Vascular Biology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Hayakari
authors.affiliation: Department of Vascular Biology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Hidemi
authors.initials: H
authors.lastname: Yoshida
authors.affiliation: Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Kawaguchi
authors.affiliation: Department of Social Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Ippei
authors.initials: I
authors.lastname: Takahashi
authors.affiliation: Department of Social Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Nakaji
authors.affiliation: Department of Vascular Biology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Tadaatsu
authors.initials: T
authors.lastname: Imaizumi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000483:Alleles; D019943:Amino Acid Substitution; D030541:Databases, Genetic; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006367:HeLa Cells; D006801:Humans; D042541:Intracellular Space; D024101:Mitochondrial Proteins / Q000235:genetics*; D011070:Poly I-C / Q000494:pharmacology; D020641:Polymorphism, Single Nucleotide; D021381:Protein Transport; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C505371:MAVS protein, human; D024101:Mitochondrial Proteins; D011070:Poly I-C