ROLE OF MURINE LEUKEMIA VIRUS IN AUTOIMMUNITY

描述(改编自申请人的摘要)：逆转录病毒已被 与人类和小鼠自身免疫性疾病有关，尽管有确凿证据 目前尚缺乏这些逆转录病毒导致自身免疫状态的证据。小鼠 白血病病毒(MuLV)是一种内源性表达的逆转录病毒。 在自身免疫小鼠中发现了含有MuLV产物的免疫复合体。 也发现了MuLV转录本的异常表达。建议进行的研究 在这个应用程序中将检验MuLV或免疫反应的假设 TO-MuLV在携带H5N1病毒的小鼠自身免疫发展中的作用 LPR突变。 申请人已证明存在至少两个潜在的小说 C3HLPR小鼠B细胞产生的传染性逆转录病毒 但在野生型或MRL LPR小鼠中检测不到。病毒血症开始出现 在大约三个月大的时候就可以检测到，这表明要么病毒可能 是重组的(如在AKR系统中)，或者可能是内源性逆转录病毒 它通常在转录上是沉默的，但其表达是被诱导的 其次是自身免疫性疾病的发展和 多克隆免疫激活。 该提案的第一个目标是确定病毒的核酸序列。 新型逆转录病毒。初步数据显示成功克隆和 表达的逆转录病毒的测序。第二个目标是研究 该逆转录病毒在不同类型小鼠不同组织中的表达 遗传背景。第三个目标是将 对逆转录病毒的抗体反应与产生自身抗体和 以确定免疫中是否存在抗逆转录病毒抗体 来自病态肾脏的复合体。

DESCRIPTION (adapted from applicant's abstract): Retroviruses have been associated with human and murine autoimmune disease, although definitive proof that these retroviruses cause the autoimmune state is lacking. Murine leukemia viruses (MuLV) are retroviruses that may be endogenously expressed. Immune complexes containing MuLV products are found in autoimmune mice. Abnormal expression of MuLV transcripts has also been found. Studies proposed in this application will test the hypothesis that MuLV or the immune response to MuLV plays a role in the development of autoimmunity in mice carrying the lpr mutation. The applicant has demonstrated the existence of at least two potentially novel infectious retroviruses which appear to be produced by B cells of C3H lpr mice but cannot be detected in wild type or MRL lpr mice. Viremia begins to be detectable at about three months of age, suggesting that either the virus may be a recombinant (as in the AKR system), or could be an endogenous retrovirus which is normally transcriptionally silent, but whose expression is induced secondarily as a result of the development of autoimmune disease and polyclonal immune activation. The first aim of the proposal is to determine the nucleic acid sequence of the novel retroviruses. Preliminary data indicates successful cloning and sequencing of an expressed retrovirus. The second aim is to study the expression of this retrovirus in different tissues from mice of different genetic backgrounds. The third aim is to correlate the expression of the antibody response to the retrovirus with the production of autoantibodies and to determine whether the anti-retrovirus antibodies are present in immune complexes from diseased kidneys.