Mashimo T, Simon-Chazottes D, Guénet J-L
Institute of Laboratory Animals, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Curr Top Microbiol Immunol. 2008;321:85-100. doi: 10.1007/978-3-540-75203-5_4.
Mouse susceptibility to experimental infections with flaviviruses is significantly influenced by a cluster of genes on chromosome 5 encoding a family of proteins with enzymatic properties, the 2'-5' oligoadenylate synthetases (OAS). Positional cloning of the locus in question has revealed that susceptibility of laboratory inbred strains to this class of virus is associated with a nonsense mutation in the gene encoding the OAS1B isoform. Analysis of the molecular structure of the cluster in different mammalian species including human indicates that the cluster is extremely polymorphic with a highly variable number of genes and pseudogenes whose functions are not yet completely established. Although still preliminary, a few recent observations also substantiate a possible role for OAS1 in human susceptibility to viral infections (West Nile virus, SARS, etc.) and its possible involvement in some other diseases such as type 1 diabetes and multiple sclerosis. Finally, convergent observations indicate that the molecules encoded by the 2 '-5' OAS cluster might be involved in other fundamental cellular functions such as cell growth and differentiation, gene regulation, and apoptosis.
小鼠对黄病毒实验性感染的易感性受到5号染色体上一组基因的显著影响，这些基因编码具有酶活性的一类蛋白质，即2'-5'寡腺苷酸合成酶（OAS）。对相关基因座的定位克隆表明，实验室近交系对这类病毒的易感性与编码OAS1B亚型的基因中的一个无义突变有关。对包括人类在内的不同哺乳动物物种中该基因簇分子结构的分析表明，该基因簇具有极高的多态性，基因和假基因数量高度可变，其功能尚未完全明确。尽管仍处于初步阶段，但最近的一些观察结果也证实了OAS1在人类对病毒感染（西尼罗河病毒、非典等）的易感性中可能发挥的作用，以及它可能参与其他一些疾病，如1型糖尿病和多发性硬化症。最后，一致的观察结果表明，2'-5'OAS基因簇编码的分子可能参与其他基本的细胞功能，如细胞生长和分化、基因调控和细胞凋亡。
