RETROVIRUS-INDUCED IMMUNE & NEURAL DISORDERS-AIDS MODEL

逆转录病毒-小鼠模型的可用性， 模拟艾滋病和艾滋病相关疾病的病因， 逆转录病毒将非常有用，因为迫切需要 了解这些病毒感染如何损害宿主的免疫力， 神经系统 因此，我们建议使用鼠逆转录病毒MOMULV-tsl，其引起 严重的免疫和神经系统功能障碍， 一系列具有许多共同特征的疾病的发病机制 人类逆转录病毒引起的疾病。我们将尝试I）确定 通过研究TS 1的免疫抑制特性的性质 ts 1感染对T和B淋巴细胞的影响。（二）确定 胸腺在TS 1诱导的发病机制中的作用 胸腺切除小鼠以及抗thy-1抗体消除T细胞， BALB/c小鼠，以确定是否需要完整的T细胞。第三章） 确定巨噬细胞在ts 1诱导的疾病中的作用， 二氧化硅处理对巨噬细胞的损害。（四）确定 TS-1诱导疾病发病机制中的组织病理学损伤 通过研究病毒从感染部位传播的机制， 对淋巴和神经系统的感染以及 淋巴器官和CNS中的病变发展。（五）确定 赋予免疫抑制特性的遗传决定子 ts 1和MOMULV-TB之间的重组构建体。 所提出的研究应产生定义明确的MuLV小鼠模型，用于 进一步研究逆转录病毒诱导的 免疫缺陷和神经病。此外，这些研究还可以 加深我们对复杂的双向互动的理解 免疫系统和神经系统之间的联系

The availability of a retrovirus-mouse model which in whole or in part mimics the etiology of AIDS and AIDS related diseases induced by human retroviruses will be very useful because of the pressing need to understand how these virus infections impair the host's immune and nervous systems. We therefore propose to use a murine retrovirus, MOMULV-tsl, which causes both severe immune and nervous system dysfunctions to study the pathogenesis of a spectrum of disorders that has many features in common with human retrovirus-induced diseases. We will attempt to I) Determine the nature of the immuno-suppressive properties of ts1 by investigating the effect of ts1 infection on T and B lymphocytes. II) Determine the role of the thymus in the ts1-induced pathogenesis by using nude and thymectomized mice as well as anti-thy-1 antibody to abolish T cells in BALB/c mice to determine whether intact T cells are required. III) Determine the role of macrophages in the ts1 -induced diseases by impairment of macrophages with silica treatment. IV) Determine the histopathological lesion in the pathogenesis of the ts1- induced diseases by studying the mechanism(s) by which the virus spread from the site of infection to the lymphoid and nervous systems and the mechanism(s) of lesion development in the lymphoid organs and the CNS. V) Identify the genetic determinant(s) which confer the immunosuppressive properties on ts1 by recombinant constructs between ts1 and MOMULV-TB. The studies proposed should result in a well defined MuLV-mouse model for further investigation of the molecular mechanism(s) of retrovirus induced immuno-deficiency and neuropathy. Furthermore, these studies may also enhance our understanding of the complex bidirectional interaction between the immune and nervous systems.