Specific ligation of the HIV-1 viral envelope protein gp120 on human CD34+ bone marrow-derived progenitors.
The precise mechanisms of hematologic abnormalities observed during HIV infection remain unknown. In vitro experiments performed by various authors concerning the HIV toxicity on bone marrow-derived precursors did not allow them to determine whether this toxicity could be mediated through direct or non-direct effects, since it is today unclear if gp120 possesses a direct hematotoxic effect on human bone marrow progenies. The aim of our study was to determine whether labelled gp120 could specifically bind to the membrane of purified human normal CD34+ cells and to investigate the in vitro effect of the gp120 on their growth. To answer these questions, human CD34+ cells were purified from normal bone marrow samples, then labelled with monoclonal antibodies directed either against CD4 antigen or CD34 antigen and/or with FITC labelled gp120 and analyzed by FACS. Our results demonstrate the presence of about 5% of CD4+CD34+ cells and of nearly 12% of CD34+gp120+ precursors. Together with our results concerning the in vitro inhibitory effect of gp120 on the growth of the same purified CD34+ precursors, our data demonstrated the direct hematotoxic activity of HIV-derived gp120 and the possible HIV infection of hematopoietic progenitors through the interaction of gp 120 with CD34+ cell surface.
Arock
M
M
Laboratory of Hematology, Faculty of Pharmacy, Paris, France.
Dedenon
A
A
Le Goff
L
L
Michel
A
A
Missenard
G
G
Debré
P
P
Guillosson
J J
JJ
D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis*; D018952:Antigens, CD34; D001854:Bone Marrow Cells; D015704:CD4 Antigens / Q000032:analysis / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003864:Depression, Chemical; D005434:Flow Cytometry; D015699:HIV Envelope Protein gp120 / Q000378:metabolism* / Q000494:pharmacology; D015497:HIV-1; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D016130:Immunophenotyping; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018952:Antigens, CD34; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D011994:Recombinant Proteins