Immune control of SIVagm replication in vivo

亚洲猕猴在感染非洲本土感染的慢病毒后会患上一种类似艾滋病的疾病 非人灵长类动物。然而，尽管非洲猴子坚持终生，但仍未患上疾病 感染同样的病毒。对自然环境的致病机制有清晰的认识 非洲猴子对慢病毒引起的疾病的抵抗力可能支持目前开发艾滋病的策略 或者为艾滋病毒感染的新治疗方式提供洞察力。 在这项建议中，我们将利用感染SIVagm的两个非洲绿猴物种的感染来 研究这一现象。利用单抗诱导的CD8+淋巴细胞耗竭模型 和我们之前开发的B细胞，我们将评估适应性免疫反应对 这些物种对疾病的天然抵抗力。 具体来说，我们会： 1.确定CD8+淋巴细胞介导的获得性免疫反应在调控中的作用 非洲绿猴的SIVagm病毒血症和疾病进展。 2.通过以下方式确定体液免疫反应在影响相同感染过程中的作用 B淋巴细胞耗竭。 3.评估废除细胞和体液适应性免疫反应是否会影响 非洲绿猴SIVagm感染的病程。

Asian macaques develop an AIDS-like disease upon infection with lentiviruses that endemically infect African nonhuman primates. However, African monkeys fail to develop disease despite persistent and life-long infection with the same viruses. A clear understanding of the mechanisms responsible for the natural resistance of African monkeys to lentivirus-induced disease might support current strategies to develop AIDS vaccines or provide insight into new treatment modalities for HIV infection. In this proposal, we will utilize the infection of two African green monkey species infected with SIVagm to study this phenomenon. Using the models of monoclonal antibody-induced depletion of CD8+ lymphocytes and B cells which we developed previously, we will assess the role of adaptive immune responses to the natural resistance to disease seen in these species. Specifically, we will: 1. Determine the role of adaptive immune responses mediated by CD8+ lymphocytes in controlling SIVagm viremia and disease progression in African green monkeys. 2. Determine the role of humoral immune responses in affecting the course of the same infections by depletion of B lymphocytes. 3. Assess whether abolishing both cellular and humoral adaptive immune responses will affect the course of SIVagm infection of African green monkeys.