NDLI: Bone marrow CD34+ cells and megakaryoblasts secrete β-chemokines that block infection of hematopoietic cells by M-tropic R5 HIV

Content Provider	PubMed Central
Author	Majka, Marcin Tomasz, Rozmyslowicz Lee, Benhur Murphy, Samuel L. Pietrzkowski, Zbigniew Gaulton, Glen N. Silberstein, Leslie Ratajczak, Mariusz Z.
Copyright Year	1999
Abstract	CD34+ cells are nonpermissive to infection by HIV strains X4 and R5, despite the fact that many CD34+ cells express high levels of the viral receptor protein CD4 and the coreceptor CXCR4 on their surface. In these cells, the co-receptor CCR5 protein, which, like CXCR4, is a chemokine receptor, is detected mainly intracellularly. We hypothesized that CD34+ cells secrete CCR5-binding chemokines and that these factors interfere with HIV R5 interactions with these cells, possibly by binding CCR5 or by inducing its internalization. We found that human CD34+ cells and CD34+KIT+ cells, which are enriched in myeloid progenitor cells, expressed and secreted the CCR5 ligands RANTES, MIP-1α, and MIP-1β and that IFN-γ stimulated expression of these chemokines. In contrast, SDF-1, a CXCR4 ligand, was not detectable in the CD34+KIT+ cells, even by RT-PCR. Conditioned media from CD34+ cell culture significantly protected the T lymphocyte cell line PB-1 from infection by R5 but not X4 strains of HIV. Interestingly, the secretion of endogenous chemokines decreased with the maturation of CD34+ cells, although ex vivo, expanded megakaryoblasts still secreted a significant amount of RANTES. Synthesis of CCR5-binding chemokines by human CD34+ cells and megakaryoblasts therefore largely determines the susceptibility of these cells to infection by R5 HIV strains. We postulate that therapeutic agents that induce the endogenous synthesis of chemokines in human hematopoietic cells may protect these cells from HIV infection.
Related Links	http://dx.doi.org/10.1172/jci7779
Ending Page	1749
Page Count	11
Starting Page	1739
File Format	PDF
ISSN	00219738
Journal	Journal of Clinical Investigation
Issue Number	12
Volume Number	104
Language	English
Publisher	American Society for Clinical Investigation
Publisher Date	1999-12-15
Access Restriction	Open
Rights Holder	American Society for Clinical Investigation
Subject Keyword	Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Medicine

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