Pathogenetic roles of human endogenous retroviruses in autoimmune diseases

点击翻译按钮获取中文摘要

To investigate the pathogenetic roles of human endogenous retroviruses (HERVs) in autoimmune diseases, we produced transgenicrats carrying an HERV genome and analyzed the transgenic rat as a model. And we tried the cDNA gene cloning for novel HERVs from vascular endothelial cells as a target of autoimmune diseases and synovial tissues of rheumatoid arthritis. Results of this research project were described below.1. Two lines of transgenicrats carrying the full-length genome of HERV-R, which is a single copy type of HERV and expresses the env gene in several human tissues, were established. The transgene was specifically expressed at high levels in Harderian and submandibular salivary glands of the rats. Using a rabbit anti-HERV-R synthetic peptides antiserum, 85kDa of Env glycoprotein, contain about 23kDa of glycan, was detected in acinar cells of the Harderian glands. The transgene was consistently expressed in concepti from day 12 after gestation and was detected in fetuses at day 18 of gestation. By the skin transplantation experiment between the transgenic and non-transgenic rats, grafts of transgenic rats in non-transgenic rats were rejected by immunological reaction of host rats, suggesting that the 85kDa Env glycoprotein is recognized as an immunological target by non-transgenic rats. Although no disease was spontaneously developed in the transgenic rats, HERV-R-related immunological disorders may develop in the rats when the immunological tolerance against the 85kDa Env glycoprotein is broken.2. We screened cDNA libraries of human placentas, umbilical vein endothelial cells and synovial tissues of rheumatoid arthritis patients, using mixture of DNAs-related human retrovirus sequences as probes. Several clones with retrovirus sequences were detected, but we found no novel HERV sequence, yet. However, we evidenced that one HERV, which is not detected any transcription in normal tissues in previous reports, is expressed in several placentas without diseases.