This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The interaction of malaria and HIV/AIDS, often present in the same patient populations, is one of the most intriguing and little understood topics in tropical medicine today. Our studies combine well established primate models for AIDS and malaria: 1) SIV, a lentivirus that establishes a severe immunodeficiency disease in rhesus macaques and 2) Plasmodium cynomolgi, which causes a relapsing disease resembling malaria induced by P. vivax. The hypotheses underlying the proposed studies are that the relapsing malaria induced by P. cynomolgi will alter the course of simian AIDS induced by SIV in the rhesus monkey and that immunosuppression induced by SIV will alter P. cynomolgi growth or relapse. Other hypotheses underlying these studies are that infection with P. cynomolgi will alter immune responses to SIV in the rhesus monkey and that immunosuppression induced by SIV will alter immune responses to the malaria parasite. We have inoculated three groups of animals, one with SIV only, one with SIV and malaria, and one with malaria only. We were able, in this final year of the project under a new PI, to look at the response at the message level of monkeys previously infected with a different isolate of P. cynomolgi. We took hepatic biopsies before and after sporozoite-induced malaria infection, work that is ethically impossible in human patients, and isolated RNA from the hepatocytes. We hybridized the RNA to a microarray chip based on the rhesus genome (Affymetrix). The findings were presented at the American Society of Tropical Medicine and Hygiene meetings in Philadelphia in late 2007 and excited some interest. The apoptosis genes were evidently down-regulated and this may be important for designing a vaccine based on hepatic stages.
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