IN VIVO EVALUATION OF PRIMATE LENTIVIRUSES

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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.