HUMORAL AND CELLULAR IMMUNE RESPONSES AGAINST SHIV INFECTION

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 获得性免疫缺陷综合症 (AIDS) 是由一种称为人类免疫缺陷病毒 (HIV) 的病毒引起的，在过去 25 年中已导致全球数百万人死亡。感染的早期阶段对于艾滋病的最终进展至关重要。进入人体后不久，艾滋病毒就会迅速扩散到淋巴结和其他器官，并在那里复制数百万份。如果病毒在一开始就得到很好的控制，那么感染者要经过很多年才会患上艾滋病，而在感染的最初几天病毒迅速扩散的人会更快地患上艾滋病。尽管我们对人类免疫缺陷病毒疾病的理解最近取得了进展，但对控制病毒在受感染宿主中复制的实际机制仍然知之甚少。 在感染 HIV-L 的成年人中，CD4 T 细胞耗竭和 HIV-1 相关疾病的进展是进行性的。成年人能够在感染期间存活更长时间的一些原因可能是由于宿主对病毒复制的免疫控制存在差异，例如更强的 CD8 细胞毒性 T 淋巴细胞（或“杀伤性 T 淋巴细胞）”和更好的中和抗体反应，这些已被证明可以抑制 HIV 复制。 动物研究可以帮助解决人类研究、计算机模型或实验室培养皿中无法回答的关键问题。大多数动物艾滋病研究都是在猴子身上进行的。一些猴子感染了 SIV，这是一种与 HIV 非常相似的病毒，会导致类似艾滋病的疾病。 SIV 和 HIV 之间的相似之处使科学家能够测试原本无法测试的理论、疫苗和药物。 我们将与西雅图生物医学研究所（SBRI，华盛顿州西雅图）的 Leonidas Stamatatos 博士合作，纵向研究病毒免疫力的发展，以确定身体如何学习对抗 SlV。我们将特别研究病毒特异性中和抗体的产生和细胞免疫反应，例如 CD8 细胞毒性 T 淋巴细胞反应，以便将这些反应与血浆中病毒浓度的控制联系起来。通过这项研究，我们预计会看到抗病毒中和抗体反应和强烈的抗病毒细胞反应的产生增加，这些反应将模仿患者感染艾滋病毒期间观察到的免疫反应。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The Acquired Immunodeficiency Syndrome (AIDS) is caused by a virus called the human immunodeficiency virus (HIV) and has resulted over the last 25 years in millions of death worldwide. The early phase of the infection is crucial in the eventual progress toward AIDS. Soon after entering the body, HIV rapidly spreads to the lymph nodes and others organs where it makes many millions of copies of itself. If the virus could be well contained at the beginning, the infected person would develop AIDS only after many years while a person with rapid expansion of the virus in the first days of infection would develop AIDS much sooner. Despite recent progress in our understanding of Human Immunodeficiency Virus disease the actual mechanisms responsible for controlling the replication of the virus in the infected host remain poorly understood. CD4+ T cell depletion and the progression of HIV-1-related diseases are progressive in adults infected with HlV-L Some of the reasons why adults are able to longer survive over the time of the infection may be due to differences in the host immune control of virus replication such as the stronger presence of CD8 cytotoxic T lymphocytes (or "killer T lymphocytes) and a better neutralizing antibody response, that have been shown to inhibit HIV replication. Animal studies can help address critical questions that cannot be answered in human studies, in computer models or laboratory dishes. Most animal AIDS research is conducted with monkeys. Some monkeys are infected with SIV, a virus very similar to HIV that causes an AIDS-like disease. The similarities between SIV and HIV allow scientists to test theories, vaccines, and medications that could otherwise never by tested. In collaboration with Dr. Leonidas Stamatatos from the Seattle Biomedical Research Institute (SBRI, Seattle WA), we will investigate the development of immunity to the virus longitudinally to determine how the body learns to fight SlV. We will particularly investigate the generation of virus-specific neutralizing antibodies and cellular immune responses such as the CD8 cytotoxic T lymphocyte responses in an effort to correlate these responses with control of virus concentration in the plasma. With this study, we are expecting to see an increased production of anti-virus neutralizing antibody responses and strong anti-viral cell responses that will mimic the immune responses observed during HIV infection in patient.