The limited infectability by R5 HIV of CD34+ cells from thymus, cord, and peripheral blood and bone marrow is explained by their ability to produce β-chemokines

Objective The resistance of human bone marrow (BM) CD34+ cells to human immunodeficiency virus (HIV) infection is at this point not fully understood. Recently we reported that the chemokines MIP-1α, MIP-1β, and RANTES secreted by BM-derived CD34+ cells may compete with the macrophagotropic HIV (R5 HIV) strain for the CCR5 coreceptor. Materials and Methods In this study we extended our previous observations and examined various lympho-hematopoietic CD34+ cells isolated from thymus (Th), cord blood (CB), mobilized peripheral blood (mPB), and BM for the expression of β-chemokines binding to CCR5, i.e., MIP-1α, MIP-1β, RANTES, MCP-2, MCP-3, and MCP-4, and the α chemokine SDF-1 (binding to CXCR4) as these chemokines may compete with the R5 and X4 HIV strains, respectively, for entry into cells. Results We found that Th-, CB-, mPB-, and BM-derived CD34+ cells express mRNA transcripts for all the β-chemokines tested but not for SDF-1. Using sensitive ELISA assays we found that although MIP-1α and MIP-1β proteins were secreted by all the lympho-hematopoietic CD34+ cells tested, RANTES was detectable only in media conditioned by BM- and CB-derived CD34+ cells and not Th-derived cells. However, media conditioned by BM-, mPB- and Th-derived CD34+ cells protected the T lymphocytic cell line (PB-1) from infection by the R5 but not the X4 HIV strain. Conclusions Hence this study demonstrates that β-chemokines are secreted by lympho-hematopoietic CD34+ cells originating from various sources and that these endogenously secreted chemokines may limit entry of the R5 HIV strain into the cells by competing for the CCR5 coreceptor.