Ogasawara H, Hishikawa T, Sekigawa I, Hashimoto H, Yamamoto N, Maruyama N
Department of Internal Medicine aind Rheumatology, Juntendo University School of Medicine, Tokyo, Japan.
Autoimmunity. 2000;33(1):15-21. doi: 10.3109/08916930108994105.
Human endogenous retroviruses (HERV) have emerged as a possible cause of systemic lupus erythematosus (SLE). We previously detected serum antibodies to the gag region of HERV clone 4-1 in patients with SLE, but not in normal volunteers. In the present study, we detected clone 4-1 messenger RNA (mRNA) in peripheral blood mononuclear cells (PBMC) from SLE patients and performed sequence analysis of the cDNA or genomic DNA from clone 4-1 in these patients. Clone 4-1 mRNA was detected in all of the SLE patients tested, although it was not found in normal controls. Sequence analysis of clone 4-1 in these SLE patients revealed inactivation of the stop codons in part of the gag region. In addition, a computer search of current sequence libraries revealed that the clone 4-1 gag genomic DNA from SLE patients was more highly homologous with the clone 4-1 sequence in chromosome 11 from normal individuals when compared with the sequence of clone 4-1 integrated in the other chromosomes. It is possible that transcription of clone 4-1 from chromosome 11 occurs in SLE, and that the stop codon inactivation contributes to the translation of clone 4-1 gag proteins in patients with this disease.
人类内源性逆转录病毒(HERV)已成为系统性红斑狼疮(SLE)的一个可能病因。我们之前在SLE患者中检测到针对HERV克隆4-1 gag区域的血清抗体,但在正常志愿者中未检测到。在本研究中,我们在SLE患者的外周血单个核细胞(PBMC)中检测到克隆4-1信使核糖核酸(mRNA),并对这些患者中克隆4-1的互补脱氧核糖核酸(cDNA)或基因组脱氧核糖核酸(DNA)进行了序列分析。在所有检测的SLE患者中均检测到克隆4-1 mRNA,而在正常对照中未发现。对这些SLE患者中克隆4-1的序列分析显示,gag区域部分的终止密码子失活。此外,对当前序列文库的计算机搜索显示,与整合在其他染色体上的克隆4-1序列相比,SLE患者的克隆4-1 gag基因组DNA与正常个体11号染色体上的克隆4-1序列具有更高的同源性。有可能在SLE中发生了11号染色体上克隆4-1的转录,并且终止密码子失活有助于该病患者中克隆4-1 gag蛋白的翻译。