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.Our laboratory recently showed that human tissue mast cells which develop from peripheral blood progenitors can serve as long-lived reservoirs of persistent HIV infection. A unique feature of this cellular reservoir is that only circulating progenitor mast cells (prMCs) are susceptible to infection whereas, mature tissue resident mast cells are HIV-infection resistant. Although in the absence of allergy or co-infection, prMCs are only susceptible to R5-tropic HIV. We showed that cross-linked IgE enhances CXCR4 expression and susceptibility of prMCs to X4-tropic HIV in vitro. To address the significance of these findings in the clinical setting of HIV-schistosomiasis co-infections, we characterized the effect of schistosome soluble egg antigen (SEA), which binds non-antigenspecific IgE, on chemokine receptor (CR) expression and on the susceptibility of IgE-primed rhesus prMCs (RhprMCs) to X4-tropic SIV. RhprMCs were derived from CD34+ progenitor stem cells isolated from rhesus bone marrow then cultured in serum free medium supplemented with recIL-6 and stem cell factor. After 3-4 weeks in culture, RhPrMCs were positive for mast cell tryptase, IgE-receptor, CD117 and mast cell beta-hexosaminidase and low level expression of CXCR4 mRNA. We found that pretreatment of RhprMC with SEA (0.4-40 ug/ml) for 24 hrs induced an IgE-dependent increase in both CXCR4 (1000 fold) and CD4 (10-20 fold) expression relative to controls by real-time PCR. In contrast, SEA alone did not induce increases in CXCR4, CD4, or CCR5 expression, suggesting an important role for IgE cross-linking in this system. SEA/IgE pretreatment also resulted in a significant concomitant increase (1000 fold relative to controls) in infection of RhprMCs with X4-tropic SHIV33a as shown by real-time PCR measurement of SHIV strong stop cDNA. These data indicate that the rhesus model can be used to characterize how retroviral-schistosomiasis co-infections can create and expand mast cell reservoirs of persistent virus infection.
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