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Blood, Vol. 93 No. 4 (February 15), 1999:
pp. 1145-1156
Coreceptor/Chemokine Receptor Expression on Human Hematopoietic
Cells: Biological Implications for Human Immunodeficiency Virus-Type
1 Infection
Benhur Lee,
Janina Ratajczak,
Robert W. Doms,
Alan M. Gewirtz, and
Mariusz Z. Ratajczak
From the Department of Medicine and the Department of Pathology and
Laboratory Medicine, Hospital of the University of Pennsylvania,
Philadelphia, PA.
The recent discovery of chemokine receptors as coreceptors for human
immunodeficiency virus-type 1 (HIV-1) entry offers new avenues for investigating the pathogenesis of acquired immunodeficiency syndrome (AIDS)-related cytopenias. To this end, we sought to (1)
phenotype human hematopoietic cells for CD4 and the HIV-1 coreceptors
CXCR4, CCR5, CCR3, and CCR2b; (2) correlate CD4 and chemokine receptor
expression with their susceptibility to HIV-1 infection; and
(3) examine any potential interplay between inflammatory cytokines
released during HIV-1 infection and regulation of chemokine receptor
expression. Fluorescence-activated cell sorting (FACS) analysis of bone
marrow mononuclear cells (BMMNC), cells derived from serum-free
expanded hematopoietic lineages (colony-forming unit-granulocyte-macrophage [CFU-GM], colony-forming
unit-megakaryocyte [CFU-Meg], and burst-forming unit-erythroid
[BFU-E]), and CD34+ cells showed
differential expression of chemokine receptors and CD4 with some
lineage specificity. Significantly, FACS-sorted CXCR4+/CD34+ cells had the same clonogeneic
potential as CXCR4 /CD34+ cells. Reverse
transcriptase-polymerase chain reaction (RT-PCR) analysis of
FACS-sorted human candidate stem cells (HSC; CD34+,
c-kit+, Rho123low) showed the presence of
CXCR4 mRNA but not CD4 mRNA. Infection studies with HIV-1
Env-pseudotyped luciferase reporter viruses indicated that X4 Env
(CXCR4-using) pseudotypes infected megakaryocytic cells, whereas R5 Env
(CCR5-using) pseudotypes did not. Similarly, R5 but not X4
Env-pseudotyped viruses infected granulocyte-macrophage cells in a
CD4/CCR5-dependent manner. Erythroid cells were resistant to R5 or X4
viral infection. Finally, we found that -interferon treatment
upregulated CXCR4 expression on primary hematopoietic cells. In
summary, the delineation of chemokine receptor expression on primary
hematopoietic cells is a first step towards dissecting the
chemokine-chemokine receptor axes that may play a role in hematopoietic
cell proliferation and homing. Furthermore, susceptibility of
hematopoietic cells to HIV-1 infection is likely to be more complicated
than the mere physical presence of CD4 and the cognate chemokine
receptor. Lastly, our results suggest a potential interplay between
-interferon secretion and CXCR4 expression.

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