HUMORAL AND CELLULAR IMMUNE RESPONSES AGAINST SHIV INFECTION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 获得性免疫缺陷综合症(艾滋病)是由一种名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。感染的早期阶段对艾滋病的最终进展至关重要。在进入人体后不久，艾滋病毒迅速传播到淋巴和其他器官，在那里它自己复制了数百万份。如果病毒在一开始就得到很好的控制，感染者只会在很多年后才会患上艾滋病，而在感染的第一天病毒迅速扩张的人会更快地患上艾滋病。尽管我们对人类免疫缺陷病毒病的了解最近取得了进展，但控制病毒在受感染宿主中复制的实际机制仍然知之甚少。 在感染艾滋病毒的成人中，CD4T细胞耗尽和HIV-1相关疾病的进展是进行性的。一些成年人能够在感染后更长时间存活的原因可能是由于宿主对病毒复制的免疫控制的不同，例如CD8细胞毒性T淋巴细胞(或称“杀手T淋巴细胞”)的存在更强，以及更好的中和抗体反应，这已被证明可以抑制艾滋病毒的复制。 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，会导致一种类似艾滋病的疾病。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(西雅图生物医学研究所，西雅图)的Leonidas Stamatos博士合作，纵向研究对病毒的免疫发展，以确定身体是如何学习对抗SLV的。我们将特别研究病毒特异性中和抗体和细胞免疫反应的产生，如CD8细胞毒性T淋巴细胞反应，以努力将这些反应与控制血浆中的病毒浓度相关联。通过这项研究，我们预计将看到抗病毒中和抗体反应和强大的抗病毒细胞反应的产生增加，这些反应将模仿患者感染HIV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.