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。子项目和 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。 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。 猴-人免疫缺陷病毒-1157ipd3N4（SHIV-1157 ipd 3 N4）是一种嵌合病毒，来源于亲本病毒（SHIV-1157 i），一种由表达HIV C进化枝env的SIVmac 239和相关辅助基因达特、vpu和Rev组成的分子克隆。 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。 该病毒专属于R5嗜性，在恒河猴PBMC中以及直肠内接种的中国和印度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-细胞免疫反应的猕猴nemestrina，使这支C SHIV可能作为一个挑战病毒在未来的疫苗研究，在这个物种。

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.