IN VIVO EVALUATION OF PRIMATE LENTIVIRUSES

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。 当慢病毒株出现时，重要的是确定每种病毒在特定的非人类灵长类物种中的传染性、致病性和最小感染量，然后才能用于疫苗试验或治疗试验。该项目旨在允许慢病毒在体内进行测试。 HIV-1分支C病毒占全球所有感染病例的50%以上。因此，在候选艾滋病疫苗的背景下研究这一亚型的机会特别宝贵。猴-人类免疫缺陷病毒-1157ipd3N4(SIV-1157ipd3N4)是由表达HIV-C env的SIVmac239及其相关辅助基因TAT、VPU和Rev.组成的分子克隆，是由亲本病毒(SIV-1157i)衍生的嵌合病毒。其中一只猴子的基因组DNA被扩增以产生一个晚期前病毒克隆，其中一个额外的核因子-kB结合位点被设计到其中以增加复制能力。这种病毒只有R5嗜性，在恒河猴外周血单核细胞以及直肠内接种的中国和印度恒河猴体内都能有效复制。本研究旨在检测恒河猴B细胞和T细胞免疫应答的感染性和诱导能力，为该物种未来的疫苗研究提供一种新的挑战病毒。

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. When strains of lentiviruses become available, it is important to determine the infectivity, pathogenicity, and minimal infectious dose of each virus in a particular nonhuman primate species before it can be used in vaccine trails or therapeutic testing. This project is designed to allow lentiviruses to be tested in vivo. The HIV-1 clade C virus accounts for greater than 50% of all infections worldwide. Thus, the opportunity to study this subtype in the context of candidate AIDS vaccines is especially valuable. Simian-Human Immunodeficiency Virus-1157ipd3N4 (SHIV-1157ipd3N4) is a chimeric virus derived from a parent virus (SHIV-1157i), a molecular clone composed of SIVmac239 expressing HIV clade C env and the associated auxiliary genes tat, vpu, and rev. This parent virus was adapted by serial passage in rhesus monkeys. Genomic DNA from one of these monkeys was amplified to generate a late proviral clone into which an extra NF-kB binding site was engineered to increase replicative capacity. This virus was exclusively R5 tropic and replicated potently in rhesus PBMC as well as in vivo in Chinese and Indian rhesus monkeys inoculated intrarectally. The current study was undertaken to measure the infectivity and inductive ability of B- and T-cell immune responses in Macaca nemestrina so that this clade C SHIV may serve as a challenge virus in future vaccine studies in this species.