Department of Respiratory Diseases, Research Institute, National Center for Global Health and Medicine, Toyama, Shinjuku-ku, Tokyo, Japan.
Immunogenetics. 2013 Feb;65(2):107-14. doi: 10.1007/s00251-012-0663-8. Epub 2012 Nov 18.
Myxovirus resistance A (MxA) is a major interferon (IFN)-inducible antiviral protein. Promoter single-nucleotide polymorphisms (SNPs) of MxA near the IFN-stimulated response element (ISRE) have been frequently associated with various viral diseases, including emerging respiratory infections. We investigated the expression profile of MxA transcripts with distinct first exons in human bronchial epithelial cells. For primary culture, the bronchial epithelium was isolated from lung tissues with different genotypes, and total RNA was subjected to real-time reverse transcription polymerase chain reaction. The previously reported MxA transcript (T1) and a recently registered transcript with a distinct 5' first exon (T0) were identified. IFN-β and polyinosinic-polycytidylic acid induced approximately 100-fold higher expression of the T1 transcript than that of the T0 transcript, which also had a potential ISRE motif near its transcription start site. Even without inducers, the T1 transcript accounted for approximately two thirds of the total expression of MxA, levels of which were significantly associated with its promoter and exon 1 SNPs (rs17000900, rs2071430, and rs464138). Our results suggest that MxA observed in respiratory viral infections is possibly dominated by the T1 transcript and partly influenced by relevant 5' SNPs.
Mx 病毒抗性 A(MxA)是一种主要的干扰素(IFN)诱导型抗病毒蛋白。MxA 启动子中靠近 IFN 刺激反应元件(ISRE)的单核苷酸多态性(SNP)与各种病毒疾病有关,包括新兴的呼吸道感染。我们研究了具有不同第一外显子的 MxA 转录本在人支气管上皮细胞中的表达谱。对于原代培养,支气管上皮细胞从具有不同基因型的肺组织中分离出来,并对总 RNA 进行实时逆转录聚合酶链反应。鉴定了先前报道的 MxA 转录本(T1)和最近注册的具有不同 5'第一外显子的转录本(T0)。IFN-β和聚肌苷酸-聚胞苷酸诱导 T1 转录本的表达比 T0 转录本高约 100 倍,T0 转录本在其转录起始位点附近也有一个潜在的 ISRE 基序。即使没有诱导剂,T1 转录本也占 MxA 总表达的约三分之二,其水平与启动子和外显子 1 SNP(rs17000900、rs2071430 和 rs464138)显著相关。我们的结果表明,在呼吸道病毒感染中观察到的 MxA 可能主要由 T1 转录本主导,部分受相关 5' SNP 影响。