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Expression of the human immunodeficiency virus type-1 coreceptors CXCR- 4
(fusin, LESTR) and CKR-5 in CD34+ hematopoietic progenitor cells
M Deichmann, R Kronenwett and R Haas
Klinische Kooperationseinheit Molekulare Hamatologie/Onkologie, Deutsches
Krebsforschungszentrum, Heidelberg, Germany.
CD34+ hematopoietic progenitor cells were assessed for mRNA expression of
the human immunodeficiency virus type-1 (HIV-1) coreceptors CXCR-4, also
termed fusin or LESTR, and CKR-5, also called CC-CKR-5 or CCR-5. The CD34+
cells were obtained from leukapheresis products of 17 patients after
granulocyte colony-stimulating factor-supported cytotoxic chemotherapy.
Using a two-step enrichment procedure including immunomagnetic bead
separation and fluorescence-activated cell sorting, the CD34+ cells had a
median purity of 99.8%. Assessing 9 CD34+ cell samples by polymerase chain
reaction after reverse transcription (RT- PCR), CXCR-4 mRNA was found in
all samples, whereas CKR-5 mRNA was only present in 3 samples, even though
a nested PCR was used. Eight additional CD34+ cell samples were sorted
according to CD4 expression. Based on a three-color immunofluorescence
analysis, the mean relative fluorescence intensity of HLA-DR was smaller on
CD34+/CD4+ cells in comparison with CD34+/ CD4- cells. CXCR-4 mRNA was
found in 5 of 8 CD34+/CD4+ samples and in 7 of 8 CD34+/CD4- samples,
whereas CKR-5 mRNA was detected in 2 CD34+/CD4+ samples and in 1 CD34+/CD4-
cell sample. Looking at the total number of CD34+ cell samples examined,
the proportion of specimens containing CXCR-4 mRNA was 84% in comparison
with 24% of specimens positive for CKR-5 mRNA. These data suggest that
CD34+/CD4+ hematopoietic progenitor cells, including true stem cell
candidates, could be susceptible to HIV-1 infection. Considering the
relatively low incidence of CD34+ cell samples containing CKR-5 mRNA,
CD34+/CD4+ cells appear to be particularly prone for HIV-1 infection via
the CXCR-4 coreceptor. Because this chemokine receptor allows T-
cell-tropic HIV-1 strains to infect cells, CD34+ cells expressing CD4 and
CXCR-4 might be infected by HIV-1 during later stages of the disease,
following a viral phenotype switch from macrophage- to T-cell- tropic HIV-1
strains.
Volume 89,
Issue 10,
pp. 3522-3528,
05/15/1997
Copyright © 1997 by The American Society of Hematology
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