IN VIVO EVALUATION OF PRIMATE LENTIVIRUSES

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 当慢病毒株可用时，重要的是确定每种病毒在特定非人灵长类物种中的感染性，致病性和最小感染剂量，然后才能用于疫苗试验或治疗试验。 该项目旨在允许在体内测试慢病毒。 猿猴-人类免疫缺陷病毒-SF 162 P4（SHIV SF 162 P4）来源于分子克隆SHIV SF 162，这是一种嵌合病毒，含有B亚型HIV-1的CCR-5-使用原代分离株的env基因。 发现猕猴传代的储备物SHIV SF 162 P3引起CD 4+肠T细胞的急剧损失，随后逐渐耗尽外周CD 4 + T细胞。 在人PBMC中扩增来自感染SHIV SF 162 P3病毒两周后感染的猕猴的淋巴结细胞和PBMC，以产生P4储备病毒，并制备攻击储备物。 HIV-1 C分支病毒占全球所有感染的50%以上。 因此，在候选艾滋病疫苗的背景下研究这种亚型的机会特别有价值。 SHIV-1157 ipd 3 N4是一种嵌合病毒，来源于表达HIV进化枝C env和相关辅助基因达特、vpu和rev的SIVmac 239分子克隆。该亲本病毒通过在恒河猴中连续传代进行适应。 扩增来自这些猴子之一的基因组DNA以产生晚期前病毒克隆，其中额外的NF-kB结合位点被工程化以增加复制能力。 该病毒专性R5嗜性，在恒河猴PBMC和静脉内和直肠内接种的恒河猴体内有效复制。 目前的研究进行测量的感染性和诱导能力的B-和T-细胞免疫反应的阴道内途径，使这些SHIV可以作为挑战病毒在未来的疫苗研究和杀微生物剂试验中，中国恒河猴利用这种感染途径。

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.