BOVINE LENTIVIRUS AS A MODEL FOR HIV INFECTION

这项拟议的研究旨在开发类似牛免疫缺陷的 病毒(BIV)作为研究HIV致病机制的潜在模型。 BIV与HIV-1在基因和抗原性上有相似之处。小牛会 通过实验接种BIV，并进行长达5年的监测 与BIV相关的临床和病理变化年份 感染。将对受感染小牛的组织和细胞进行检查 对于大体和微观的变化。原位杂交和 免疫组织化学将被用来关联任何病理 随着病毒的存在而变化，并确定病毒的位置 感染。BIV对宿主免疫能力的影响将 使用一系列淋巴细胞、单核细胞和 中性粒细胞功能。我们将跟踪BIV的发展- 特异性抗体的存在与其病程的相关性 临床疾病。在整个实验过程中收集的血清 期间将进行BIV中和抗体的检测 对BIV感染的细胞和抗体依赖的 细胞介导的细胞毒试验。抗体效价将是 与临床和病理结果相关联，以检测 抗体在BIV感染发病机制中的可能作用 致命性病毒感染的体内后果将是 通过将BIV与牛或牛混合感染进行的研究 疱疹病毒(BHV)或牛白血病病毒(BLV)。最后，我们会 探索病毒变异作为病毒的潜在机制 坚持不懈。BIV的顺序分离株将从 感染的小牛和基因特征决定了 病毒变异的频率和程度。分离株将是 在体外具有抗原性、宿主细胞趋向性和 致病性，以便更好地了解变异的机制 选择。这项提案中概述的实验将会更好 定义动物慢病毒的生物学复杂性 很少受到关注的感染，可能 为发展和评估提供独特的机会 人和动物的治疗方法和疫苗方案 慢病毒感染。

The proposed research aims to develop bovine immunodeficiency-like virus (BIV) as a potential model for the study of HIV pathogenesis. BIV has genetic and antigenic similarities to HIV-1. Calves will be experimentally inoculated with BIV and monitored for up to five years for clinical and pathological changes associated with BIV infection. Tissues and cells from infected calves will be examined for gross and microscopic changes. In situ hybridization and immunohistochemistry will be used to correlate any pathological changes with the presence of virus and to determine sites of viral infection. The effect of BIV on host immune competence will assessed using a battery of tests for lymphocyte, monocyte and neutrophil function. We will follow the development of BIV- specific antibody and correlate its presence with the course of clinical disease. Sera collected throughout the experimental period will be assays for BIV neutralizing antibody, for antibody to BIV-infected cells and for activity in an antibody-dependent cell-mediated cytotoxicity assay. Antibody titers will be correlated with clinical and pathological findings to detect a possible role for antibody in the pathogenesis of BIV infection. The in vivo consequences of concommitant viral infections will be studied by coinfecting calves with BIV and either a bovine herpesvirus (BHV) or bovine leukemia virus (BLV). Finally, we will explore viral variation as a potential mechanism of viral persistence. Sequential isolates of BIV will be recovered from infected calves and genetically characterized to determine the frequency and extent of viral variation. Isolates will be characterized in vitro as to antigenicity, host cell tropism and pathogenicity in order to better understand mechanisms of variant selection. The experiments outlined in this proposal will better define the biological complexities of an animal lentivirus infection which has received the little attention and which may provide unique opportunities for development and evaluation of therapeutic treatments and vaccine protocols in human and animal lentivirus infections.