DEVELOPMENT OF A MONKEY MODEL FOR TESTING OF ANTIVIRAL AGENTS AGAINST HIV-1

开发用于测试 HIV-1 抗病毒药物的猴子模型

• 批准号: 3770322
• 负责人: A S KHAN
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3770322
• 关键词: AIDS therapy; Macaca nemestrina; antiviral agents; blood chemistry; cytotoxic T lymphocyte; disease /disorder model; drug screening /evaluation; helper T lymphocyte; human immunodeficiency virus 1; leukocyte count; model design /development; nonhuman therapy evaluation; polymerase chain reaction; recombinant DNA; suppressor T lymphocyte; virus DNA; virus envelope; western blottings

The human immunodeficiency virus (HIV-1) causes AIDS in man. The development of an animal model system for infection and disease by HIV-1 is essential for AIDS vaccine studies and intervention. Currently, the only animal species which can be infected by HIV-1 is the chimpanzee; however, n disease is produced. Due to the enormous cost of maintaining a chimpanzee and the fact that this cannot be a disease model, a better model was sought Based upon a report from the Washington Primate Research Center, studies were undertaken to investigate HIV-1 infection in pig-tail monkeys. Four monkeys have been inoculated with two isolates of HIV-1 which differ in their env regions: two monkeys received LAV, which is similar in its env to the laboratory adapted strain, HIV-1 IIIB; and two monkeys received a primary isolate (<4 passages) which is similar in its env region to the MN strain, which represents the majority of North American HIV-1 isolates. Th monkeys will be analyzed for infectivity as follows using blood samples collected every two weeks post-inoculation: PBLs will be prepared for viru isolation; plasma will be obtained for antibody detection by Western blot analysis; DNAs will be prepared from PBLs for analysis of viral DNA by PCR; blood will be phenotyped for CD4 and CD8; serum chemistry also will be performed. Additionally, recombinant HIV-1 DNAs are being constructed to generate a virus with an increased tropism for monkey cells. Such a virus will also b tested in vivo for its potential use in developing the monkey system for studying HIV-1 induced AIDS.

人类免疫缺陷病毒（HIV-1）在人类中引起艾滋病。 开发HIV-1感染和疾病的动物模型系统， 艾滋病疫苗研究和干预至关重要。 目前，唯一 可以被HIV-1感染的动物物种是黑猩猩;然而，n 疾病产生了。 由于饲养一只黑猩猩的巨大成本 这不可能是一个疾病模型，因此人们寻找了一个更好的模型， 根据华盛顿灵长类动物研究中心的一份报告， 为研究HIV-1感染在猪尾猴中的作用。 四 猴子已经接种了两种HIV-1分离株， 它们的env区域：两只猴子接受了LAV，LAV在其env中与 实验室适应株HIV-1 IIIB;两只猴子接受了 原代分离株（<4代），其env区域与MN相似 毒株，代表了大多数北美HIV-1分离株。 日 使用血样分析猴的感染性，如下所示 接种后每两周采集一次：将制备用于维鲁检测的PBL 分离;将获得血浆，通过Western印迹法进行抗体检测 分析;将从PBL制备DNA，用于通过PCR分析病毒DNA; 将对血液进行CD 4和CD 8表型分析;还将对血清化学进行分析。 执行。 此外，正在构建重组HIV-1 DNA，以产生一种 对猴细胞的嗜性增加的病毒。 这样的病毒也会感染B 在体内测试了其在开发猴系统中的潜在用途， 研究HIV-1引起的艾滋病。