Gourley M F, Kisch W J, Mojcik C F, King L B, Krieg A M, Steinberg A D
Cellular Immunology Section, Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculeskelatal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Tohoku J Exp Med. 1994 May;173(1):105-14. doi: 10.1620/tjem.173.105.
Retroviruses have been implicated in the pathogenesis of murine and human lupus; however, many positive findings have been followed by alternative explanations. Initial findings implicating xenotropic retroviruses were subsequently invalidated. The first solid demonstration that endogenous retroviruses mediate disease was the study of SL/Ni mice. Here budding ecotropic retroviral particles from arterial smooth muscle cells caused an antibody response to the particles with subsequent complement deposition. Our laboratory has focused on derangements in endogenous MCF retroviral expression. We found that lupus-prone NZB, BXSB and MRL strains have a marked increase in expression of Mpmv RNA in their thymuses while bone marrow expression did not differ from normal strains. Sequence analysis demonstrated mutations in the NZB endogenous retroviruses which could alter expression. A phosphorothioate antisense oligonucleotide to the initiation sequence of Mpmv caused lymphocyte activation in vivo in normal mice, providing further evidence for in vivo effects of Mpmv and potential for pathological abnormalities in lupus-prone strains.
逆转录病毒被认为与小鼠和人类狼疮的发病机制有关；然而，许多阳性发现随后都有其他解释。最初涉及嗜异性逆转录病毒的发现随后被证明是无效的。内源性逆转录病毒介导疾病的第一个确凿证据是对SL/Ni小鼠的研究。在该研究中，来自动脉平滑肌细胞的出芽亲嗜性逆转录病毒颗粒引发了针对这些颗粒的抗体反应，随后出现补体沉积。我们实验室专注于内源性MCF逆转录病毒表达的紊乱。我们发现，易患狼疮的NZB、BXSB和MRL品系的胸腺中Mpmv RNA的表达显著增加，而骨髓表达与正常品系没有差异。序列分析表明，NZB内源性逆转录病毒中的突变可能会改变表达。一种针对Mpmv起始序列的硫代磷酸酯反义寡核苷酸在正常小鼠体内引起淋巴细胞活化，为Mpmv的体内作用以及易患狼疮品系中出现病理异常的可能性提供了进一步证据。
