MOUSE MODEL FOR RETROVIRUS INDUCTION OF IMMUNODEFICIENCY

我们提议的研究的目标是理解一个模型是如何 小鼠感染逆转录病毒会导致严重的免疫缺乏症， 评估其他感染性病原体与逆转录病毒的相互作用 免疫缺陷的诱导，并证明他的小鼠疾病 是一种准确而有用的获得性免疫缺陷综合征模型 (艾滋病)。引起小鼠艾滋病的逆转录病毒是一种生态亲和性的混合物 和水貂细胞形成病灶的小鼠白血病病毒，命名为LP-BM 5MuLV。 Lp-BM-5MuLV感染敏感株小鼠可导致 细胞免疫和体液免疫的快速和可重复的丧失。无字词 裸鼠对Lp-BM5MuLV感染的大部分效应具有抵抗力。我们的 具体目的是确定T淋巴细胞在疾病中的作用 诱导，以检查多克隆B细胞激活的原因 是本病的显著特征，研究巨噬细胞功能改变 在LP-BM 5MuLV感染期间，调查淋巴因子的过度产生 并寻找自身免疫现象的证据 导致免疫功能迅速丧失。此外，我们还将 LP-BM 5MuLV感染与几种病毒相互作用的研究 机会性感染在艾滋病患者中很常见。这些实验性的 感染源包括单纯疱疹病毒I型、小鼠巨细胞病毒、念珠菌 白色念珠菌和都柏林沙门氏菌。这些研究将检查这两个增加的 LP-BM 5MuLV对这些条件致病菌的易感性 一种或多种混合感染小鼠艾滋病的感染和加速作用 这些药物和LP-BM 5-LV。正在进行的治疗性干预 将对使用环孢素A的小鼠艾滋病进行研究，试图 制定治疗艾滋病患者的策略。

The objectives of our proposed studies are to understand how a model retrovirus infection of mice leads to profound immunodeficiency disease, to evlauate the interaction of other infectious agents with the retrovirus in the induction of immunodeficiency, and to document that his murine disease is an accurate and useful model for acquired immunodeficiency syndrome (AIDS). The retrovirus that causes murine AIDS is a mixture of ecotropic and mink cell focus-forming murine leukemia viruses termed LP-BM 5 MuLV. Infection of susceptible strains of mice with LP-BM 5 MuLV leads to the rapid and reproducible loss of both cellular and humoral immunity. Athymic nude mice are resistant to most effects of LP-BM 5 MuLV infection. Our specific aims are to determine the role of T lymphocytes in disease induction, to examine the causes of the polyclonal B cell activation that is a prominent feature of the disease, to study altered macrophage function during LP-BM 5 MuLV infection, to investigate overproduction of lymphokines during the disease, and to seek evidence of autoimmune phenomena contributing to the rapid loss of immune function. In addition, we will investigate the interaction of LP-BM 5 MuLV infection and several opportunistic infections common in AIDS patients. These experimental infectious agents include herpes simplex I, murine cytomegalovirus, Candida albicans, and Salmonella dublin. These studies will examine both increased susceptibility to these opportunistic pathogens following LP-BM 5 MuLV infection and acceleration of murine AIDS by co-infection with one or more of these agents and LP-BM 5 MuLV. Therapeutic intervention in ongoing murine AIDs with cyclosporin A will be investigated in an attempt to develop a strategy for treating AIDS patients.