Chemokine receptors and the molecular basis for human immunodeficiency virus type 1 entry into peripheral hematopoietic stem cells and their progeny

There exist at least two major coreceptors for human immunodeficiency virus (HIV)-1 entry into target cells, the CXCR-4 and CCR-5 chemokine receptors for T lymphocyte-tropic and macrophage-tropic strains of HIV-1, respectivel y. Highly purified human CD34 cells derived from umbilical cord blood were shown not to express CD4, CXCR-4, and CCR-5 on their cell membranes, as ana lyzed by immunofluorescent staining and flow cytometric analyses. However, expression of these molecules was inducible when highly purified CD34 cells underwent proliferation and differentiation along myeloid cell lineages, i n the presence of suitable cocktails of hematopoietic growth factors. HIV-1 infectivity studies showed that macrophage-tropic strains of HIV-1 could e fficiently infect differentiated CD34 cells. T lymphocyte-tropic strains co uld not infect CD34 cells before or after induction of receptors and corece ptors, These data suggest that HIV-1 infection of CD34 cells and their prog eny depends on membrane expression of the critical CD4 receptor, as well as certain chemokine coreceptors.