RETROVIRUS-INDUCED IMMUNE & NEURAL DISORDERS-AIDS MODEL

部分或全部逆转录病毒小鼠模型的可用性 模仿人类引起的艾滋病和艾滋病相关疾病的病原学 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和 神经系统。 因此，我们建议使用一种小鼠逆转录病毒，MOMULV-TSL，它能引起 严重的免疫和神经系统功能障碍研究 具有许多共同特征的一系列疾病的发病机制 人类逆转录病毒引起的疾病。我们将尝试i)确定 通过研究探讨Ts1免疫抑制特性的本质 Ts1感染对T、B淋巴细胞的影响Ii)确定 胸腺在Ts1诱导的裸小鼠和小鼠胸腺损伤中的作用 胸腺切除小鼠及抗THY-1抗体对小鼠T细胞的杀伤作用 以确定是否需要完整的T细胞。Iii) 确定巨噬细胞在Ts1诱导的疾病中的作用 二氧化硅处理对巨噬细胞的损伤。四)确定 Ts1诱发疾病发病机制中的组织病理学改变 通过研究病毒从霍乱现场传播的机制(S) 淋巴和神经系统的感染及发病机制(S) 淋巴器官和中枢神经系统的病变发展。V)确定 赋予人免疫抑制特性的遗传决定因素(S) Ts1与MOMULV-TB之间的重组构建。 所提出的研究应该会导致一个明确的小鼠模型 逆转录病毒诱导分子机制的进一步研究(S) 免疫缺陷和神经病。此外，这些研究还可能 加深对复杂双向相互作用的认识 在免疫系统和神经系统之间。

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.