TRANSCRIPTOME PROFILES OF GENE EXPRESSION IN MONKEY MODELS OF HUMAN MALARIA

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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. Malaria, a mosquito borne disease, is a major global health concern and NIAID has developed an agenda that will expand research efforts, including genomic studies, on this important pathogen. P. vivax is the most common of the four human malaria parasites and infection is widespread in Asia, Latin America, the Middle East, North Africa, and the South Pacific. P. cynomolgi, used in this study, is a simian parasite closely related to, and a good model of, P. vivax. Two rhesus macaques were inoculated with sporozoites of P. cynomolgi and RNA was isolated from peripheral blood mononuclear cells (PBMCs) harvested before infection (baseline), after 8 days (liver phase), at the peak parasitemia, at the first relapse, and at the second relapse. Samples were run on a human microarray chip containing over 22,000 genes. Sample clustering, using over 3,000 differentially expressed genes, showed that samples from both monkeys clustered similarly, with baseline samples being very distinct from other samples and the first and second relapse samples being the most similar. Hierarchical clustering of the genes showed dramatic gene expression level changes on both monkeys, especially down regulation of many genes during the initial liver stages and at the peak parasitemia. Interestingly, the number of enriched genes involved in defense and immunity showed increase throughout the time course. In this study we were able to use the monkey malaria model effectively to study the transcriptome profiles of the host gene expression, since we infected malaria-na¿ve animals, and neither concomitant infections nor nutritional status were confounding factors as would be expected in human patients from malaria-endemic areas. The publication of this work has elicited considerable interest from the malaria research community and was the subject of an invited presentation to The Institute of Genomic Research in December.