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。 猴-人类免疫缺陷病毒SF162P4(SHIV SF162P4)是从分子克隆SHIV SF162衍生而来的，SHIV SF162是一种嵌合病毒，含有CCR-5的env基因，使用的是B亚型HIV-1的主要分离株。SHIV SF162P3是一种猕猴传代种群，被发现会导致肠道内CD4+T细胞的急剧丧失，随后外周CD4+T细胞逐渐枯竭。从感染SHV SF162P3病毒2周后的恒河猴的淋巴结细胞和PBMC中扩增出P4病毒株，并制备成攻毒株。 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。SHIV-1157ipd3N4是由表达HIV分支C env的SIVmac239及其相关辅助基因TAT、VPU和Rev.组成的分子克隆而来的嵌合病毒。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。该病毒仅具有R5嗜性，可在恒河猴外周血单核细胞中复制，并在静脉和直肠内接种的恒河猴体内复制。 本研究旨在通过阴道途径检测B细胞和T细胞免疫应答的感染性和诱导能力，以期在未来的疫苗研究和中国恒河猴杀微生物剂试验中利用这一途径作为攻击性病毒。

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. Simian-Human Immunodeficiency Virus-SF162P4 (SHIV SF162P4) is derived from a molecular clone, SHIV SF162, a chimeric virus that contains the env gene of a CCR-5-using primary isolate of subtype B HIV-1. A macaque-passaged stock, SHIV SF162P3 was found to cause a dramatic loss of CD4+ intestinal T cells followed by a gradual depletion of peripheral CD4+ T cells. Lymph node cells and PBMC from a macaque infected with the SHIV SF162P3 virus two weeks after infection were amplified in human PBMC to generate a P4 stock virus and a challenge stock was prepared. 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. SHIV-1157ipd3N4 is a chimeric virus derived from 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 and in vivo in rhesus monkeys inoculated intravenously and intrarectally. The current study was undertaken to measure the infectivity and inductive ability of B- and T-cell immune responses by the intravaginal route so that these SHIVs may serve as challenge viruses in future vaccine studies and microbicide trials in Chinese rhesus macaques utilizing this route of infection.