BOVINE LENTIVIRUS AS A MODEL FOR HIV INFECTION

这项研究旨在开发牛免疫缺陷样 病毒（BIV）作为研究HIV发病机制的潜在模型。 BIV与HIV-1具有遗传和抗原相似性。 小牛将 实验性接种BIV，并监测最多5 与BIV相关的临床和病理变化的年数 感染 将检查感染小牛的组织和细胞 肉眼和显微镜下的变化 原位杂交和 免疫组织化学将用于关联任何病理学 随着病毒的存在而变化，并确定病毒的位点， 感染 BIV对宿主免疫能力的影响将 使用淋巴细胞、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，并将其存在与 临床疾病 在整个实验过程中收集的血清 期间将检测BIV中和抗体， BIV感染的细胞，并在抗体依赖性 细胞介导的细胞毒性测定。 抗体滴度将为 与临床和病理结果相关，以检测 抗体在BIV感染发病机制中的可能作用。 伴随病毒感染的体内后果将是 研究通过用BIV和牛 疱疹病毒（BHV）或牛白血病病毒（BLV）。 最后我们将 探索病毒变异作为病毒感染的潜在机制 坚持不懈 BIV的连续分离株将从 感染的小牛和遗传特征，以确定 病毒变异的频率和程度。 分离株进行 在体外表征抗原性、宿主细胞嗜性和 致病性，以便更好地了解变异的机制 选择. 本提案中概述的实验将更好地 定义动物慢病毒的生物学复杂性 很少受到关注的感染， 为发展和评估提供了独特的机会， 人和动物的治疗和疫苗方案 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.