HUMORAL AND CELLULAR IMMUNE RESPONSES AGAINST SHIV INFECTION

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH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 中心，不一定是研究者的机构。 获得性免疫缺陷综合征（艾滋病）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年中导致全世界数百万人死亡。感染的早期阶段对最终发展为艾滋病至关重要。在进入人体后不久，艾滋病毒迅速扩散到淋巴结和其他器官，在那里它会复制数百万个自己。如果病毒在感染初期能得到很好的控制，受感染的人会在多年后才患上艾滋病，而在感染初期病毒迅速扩散的人，则会更快患上艾滋病。尽管我们对人类免疫缺陷病毒疾病的了解最近取得了进展，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，CD 4 + 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病毒复制的宿主免疫控制的差异，例如更强的CD 8细胞毒性T淋巴细胞的存在。（或“杀伤T淋巴细胞”）和更好的中和抗体反应，已被证明可以抑制HIV复制。 动物研究可以帮助解决在人类研究、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用猴子进行的。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之间的相似性使科学家能够测试理论，疫苗和药物，否则永远不会被测试。 与来自西雅图生物医学研究所（SBRI，西雅图WA）的Leonidas Stamatatos博士合作，我们将纵向研究对病毒的免疫力的发展，以确定身体如何学会对抗SLV。我们将特别研究病毒特异性中和抗体和细胞免疫应答（如CD 8细胞毒性T淋巴细胞应答）的产生，以将这些应答与血浆中病毒浓度的控制相关联。通过这项研究，我们期待看到抗病毒中和抗体反应和强抗病毒细胞反应的产生增加，这将模拟患者感染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.