Simian immunodeficiency virus infection of hematopoietic stem cells and bone marrow stromal cells

Using a well-characterized fetal rhesus monkey model, simian immunodeficiency virus (SIV) infection of hematopoietic stem cells (HSCs) and stromal cells was investigated to characterize bone marrow abnormalities in SIV-infected animals in vivo. Fetuses (n = 4) were inoculated in utero with pathogenic SIVmac251 using established techniques at 65 days; gestation (early second trimester), then harvested for tissues 65 days after inoculation (late third trimester), and compared with findings from controls of a comparable age (n = 11). Sorted bone marrow CD34CD38, CD34CD38, and marrow stromal cells were analyzed for the SIV genome. Results indicate that CD34CD38 HSCs were not infected, whereas the SIV genome was detected in the CD34CD38 hematopoietic cell population by PCR analysis. The SIV proviral sequence was not detected in stromal cells from SIV-infected fetuses, although SIVmac251 was found to readily infect these cells when assessed in vitro. Flow cytometric analysis revealed that stromal cells express low levels (1 in 600 total cells) of CD4 and CCR5 viral receptors, whereas CXCR4 expression was not observed. These data suggest the following: (1) SIV infection of HSCs requires some degree of differentiation for viral entry similar to findings for humans infected with HIV type 1, and (2) SIV can infect bone marrow stromal cells that express CD4 and CCR5 in vitro, but infected stromal cells are not readily found in vivo.