Ehlhardt Sandra, Seifert Markus, Schneider Johannes, Ojak Andreas, Zang Klaus D, Mehraein Yasmin
Department of Human Genetics and Department of Dermatology, Saarland University, University Hospital, Homburg/Saar, Germany.
J Rheumatol. 2006 Jan;33(1):16-23.
Despite abundance in the genome, the possible functions of human endogenous retrovirus (HERV) sequences are not well understood. The involvement of HERV in various disease conditions, such as germ cell tumors or autoimmune diseases like rheumatoid arthritis (RA), has been suggested. We investigated expression of HERV-K(HML-2) env-derived transcripts in normal and RA synovia.
We analyzed HERV-K(HML-2) expression on the mRNA and protein level by RT-PCR analysis and immunofluorescence labeling of the HERV-K(HML-2) Rec (formerly cORF) protein. We examined synovial cell cultures from normal synovia (n = 9), from patients with RA (n = 26), and osteoarthritis (OA, n = 4), and uncultured synovial tissues (RA, n = 12; normal synovia, n = 1).
HERV-K Rec protein was expressed in all normal synovial specimens, and in the majority of RA and OA cases. We demonstrate for the first time expression of HERV-K protein in synovial tissue. RT-PCR and sequence analysis of cloned RT-PCR products confirmed expression of spliced HERV-K(HML-2) env transcripts in normal and in arthritic synovia. In addition to rec mRNA, several alternatively spliced transcripts, including np9, were identified. However, different amounts of the various RT-PCR products indicate different expression levels of HERV-K(HML-2) env-derived transcripts in RA compared to normal synovia, with apparently lower expression levels in arthritic synovia.
These findings imply a physiological role of HERV-K(HML-2) Rec in synovial tissue. Differences in the expression of HERV-K env-derived transcripts in RA synovia may be caused by disease-specific changes in the general expression pattern.
尽管人类内源性逆转录病毒（HERV）序列在基因组中大量存在，但其可能的功能尚未完全明确。已有研究表明HERV参与了多种疾病状态，如生殖细胞肿瘤或类风湿关节炎（RA）等自身免疫性疾病。我们研究了HERV-K（HML-2）env衍生转录本在正常和RA滑膜中的表达情况。
我们通过逆转录聚合酶链反应（RT-PCR）分析以及对HERV-K（HML-2）Rec（以前称为cORF）蛋白进行免疫荧光标记，在mRNA和蛋白质水平上分析HERV-K（HML-2）的表达。我们检测了来自正常滑膜（n = 9）、RA患者（n = 26）和骨关节炎（OA，n = 4）的滑膜细胞培养物，以及未培养的滑膜组织（RA，n = 12；正常滑膜，n = 1）。
HERV-K Rec蛋白在所有正常滑膜标本以及大多数RA和OA病例中均有表达。我们首次证明了HERV-K蛋白在滑膜组织中的表达。RT-PCR以及对克隆的RT-PCR产物进行的序列分析证实了正常和关节炎滑膜中存在剪接的HERV-K（HML-2）env转录本。除了rec mRNA外，还鉴定出了几种可变剪接的转录本，包括np9。然而，不同数量的各种RT-PCR产物表明，与正常滑膜相比，RA中HERV-K（HML-2）env衍生转录本的表达水平不同，关节炎滑膜中的表达水平明显较低。
这些发现表明HERV-K（HML-2）Rec在滑膜组织中具有生理作用。RA滑膜中HERV-K env衍生转录本表达的差异可能是由总体表达模式中疾病特异性变化引起的。
