MOUSE MODEL FOR RETROVIRUS INDUCTION OF IMMUNODEFICIENCY

我们提出的研究的目标是了解一个模型如何 小鼠的逆转录病毒感染导致严重的免疫缺陷疾病， 评估其他感染因子与逆转录病毒的相互作用 诱导免疫缺陷，并记录他的鼠疾病 是获得性免疫缺陷综合征一个准确和有用的模型 （艾滋病）。 导致小鼠艾滋病的逆转录病毒是嗜亲性 和貂细胞病灶形成鼠白血病病毒，称为LP-BM 5 MuLV。 用LP-BM 5 MuLV感染敏感品系的小鼠， 细胞和体液免疫的快速和可再现的丧失。 无胸腺 裸鼠对LP-BM 5 MuLV感染的大多数效应具有抗性。 我们 具体目标是确定T淋巴细胞在疾病中的作用 诱导，以检查多克隆B细胞活化的原因， 是该疾病的一个突出特征，研究巨噬细胞功能的改变 在LP-BM 5 MuLV感染期间，研究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，我们将 研究LP-BM 5 MuLV感染与几种 艾滋病患者常见的机会性感染。 这些实验 感染因子包括单纯疱疹I、鼠巨细胞病毒、念珠菌 白色念珠菌和都柏林沙门氏菌。 这些研究将检查增加的 LP-BM 5 MuLV后对这些机会性病原体的敏感性 通过与一种或多种病毒共感染来感染和加速鼠AIDS 和LP-BM 5 MuLV。 正在进行的治疗干预 将研究用环孢菌素A治疗的鼠AIDS， 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.