Development of prophylactic strategies to prevent infection of HIV-1 requires a suitable virus/animal model Chimeric simian-human immunodeficiency viruses (SHIVs) have been shown to productively infect non-human primates and to induce AIDS-like disease in infected animals. To test prophylactic strategies against HIV-1 clade C in vivo (Projects 2 and 3), the construction of a chimeric SHIV that expresses and HIV-1 clade C envelope from a primary patient isolate as essential. DNA-based vaccines, with their ability to express antigens in vivo, represent a new approach to protect against AIDS virus infections. DNA vaccines are able to raise humoral and cell-mediated immune responses against HIV. Thus, we propose to construct a recombinant DNA vaccine expressing HIV-1 clade C env, and to test its ability in vivo to raise a protective immune response (Project 3). Other retrovirusal infections (SRV/D, STLV-I) can confound experiments with SHIV. Core B will screen all experimental animals (Projects 2 and 3) for these viruses. Plasma viral RNA load is a key parameter in disease progression of lentiviral infection. We have developed a very sensitive real-time RT-PCR in our laboratory that will be used to monitor viral plasma kinetics in experimental animals (Projects 2 and 3). In addition, DNA pro-viral loads will be quantified by DNA PCR in experimental animals. The overall goal of Core B is to provide molecular biology expertise and support for projects 2 and 3: (1) Generation of chimeric SHIV containing env of a recently transmitted pediatric HIV-1 clade C isolate (SHIVenvC) (2) Generation of plasmids expressing codon-optimized HIV-1 clade C env and SIV gag-pol (3) Monitoring of experimental animals for other retrovirus infections (4) Monitoring of viral kinetics of SHIVenvC
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