Alteration of Antiviral Signalling by Single Nucleotide Polymorphisms (SNPs) of Mitochondrial Antiviral Signalling Protein (MAVS).
Alteration of Antiviral Signalling by Single Nucleotide Polymorphisms (SNPs) of Mitochondrial Antiviral Signalling Protein (MAVS).
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DOI：
10.1371/journal.pone.0151173
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Imaizumi T
中科院分区：
文献类型：
--
作者：
Xing F;Matsumiya T;Hayakari R;Yoshida H;Kawaguchi S;Takahashi I;Nakaji S;Imaizumi T
遗传变异与疾病有关。单核苷酸多态性（single nucleotide polymorphism，SNP）作为一种具有一定规律性和频率的遗传变异，因其重要的研究价值和实际应用价值而受到越来越多的关注。线粒体抗病毒信号蛋白（MAVS）作为视黄酸诱导基因-I（RIG-I）样受体（RLR）的常见接头分子，其可以识别外源RNA，包括病毒RNA，导致I型干扰素（IFN）的诱导。因此，MAVS被认为是抗病毒天然免疫中的关键分子。我们推测MAVS的遗传变异可能导致对传染病的易感性。为了评估基于MAVS变异的病毒感染风险，我们测试了来自国家生物技术信息中心（NCBI）数据库的12个非同义MAVS编码区SNP的影响，这些SNP导致氨基酸取代。我们发现其中5个SNP表现出功能改变。此外，四种导致抑制性免疫反应，一种产生相反的效果。总共有1，032份从大规模检查中获得的人类基因组样本在这五个SNP上进行了基因分型。然而，没有检测到纯合或杂合变异。我们假设这五个SNPs在日本人群中不存在，并且这种MAVS变异可能导致严重的免疫疾病。
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.