The goal of this R24 application is to generate whole transcriptome reference databases for several immune cell types at baseline and during HIV and SIV infection, with emphasis on the comparative models of pathogenic and non-pathogenic infections. We envision that these databases will serve as novel and valuable resources for studies of AIDS pathogenesis, prevention, and therapeutics. The project is an outgrowth of the revolutionary advances associated with next-generation sequencing, and leverages the complementary expertise of Dr. Katze in systems biology and bioinformatics and of Dr. Silvestri in AIDS research.
In Aim 1, we will generate baseline reference transcriptomes for several key immune cell subsets (""""""""immunome"""""""") in four primate species (humans, rhesus macaques, RMs, sooty mangabeys, SMs, and African green monkeys, AGMs) that represent the most used models for AIDS research. We will sort cell types from each species, and we will isolate RNA that will be comprehensively sequenced by.the Katze lab.
In Aim 2, we will generate reference transcriptomes for the same immune cells but in the context of acute SIV infection in the pathogenic RM and the non-pathogenic AGM models.
In Aim 3, we will generate reference transcriptomes for the same immune cells but in the context of chronic HIV and SIV infection in humans, RMs, SMs, and AGMs. We believe that the potential impact of these resources is substantial. Resource applications include: (i) improvements to gene models for already sequenced species and assistance for genome assembly/annotation for new species (i.e., SMs and AGMs);(ii) development of tools (e.g., species-specific gene probes or microarrays) for AIDS-related systems biology research;(iii) investigation ofthe interaction between lentiviruses and the immune system during acute arid chronic infection. The obtained reference transcriptome information will be used to generate new hypotheses, design new experiments, and advance basic, translational, and clinical research in the fields of HIV prevention and therapy.
We believe establishment of a data set providing a comprehensive range of immune cell types and models of pathogenic and non-pathogenic HIV/SIV infections will serve as valuable new resources for a large number of in vitro and in vivo studies of AIDS pathogenesis, prevention, and therapeutics.
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