The CD4 receptor plays essential but distinct roles in HIV‐1 infection and induction of apoptosis in primary bone marrow GPIIb/IIIa+ megakaryocytes and the HEL cell line

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Abstract
Summary. We investigated whether cells belonging to the megakaryocyte lineage could be infected in vitro with human immunodeficiency virus type‐1 (HIV‐1). Primary GPIIb/IIIa+ bone marrow (BM) cells and HEL continuous cell line were first phenotypically characterized for the presence of megakaryocytic markers and CD4 antigen, then challenged in vitro with the laboratory strain IIIB of HIV‐1. Both GPIIb/IIIa+ BM and HEL cells expressed significant levels of CD4 receptor (+ and CD4 cells. Although unfractionated and CD4+ HEL cells were productively infected with HIV‐1, CD4 HEL cells could not be infected. Infection of HEL cells did not induce gross cytotoxic effects or a significant increase of apoptosis. On the other hand, treatment of unfractionated or CD4+ HEL cells with cross‐linked recombinant env gp120 or Leu3a anti‐CD4 monoclonal antibody markedly (P< 0.01) increased the degree of apoptosis with respect to HEL cells infected with HIV‐1 or treated with cross‐linked gag p24 or anti‐GPIIb/IIIa antibody. Taken together, these data indicate that the CD4 receptor represents the main route of infection in cells belonging to the megakaryocytic lineage. Moreover, an inappropriate engagement of CD4 by either free env gpl20 or anti‐CD4 monoclonal antibody could be more relevant than a direct infection with HIV‐1 in the induction of the frequent BM megakaryocyte abnormalities found in HIV‐1 seropositive thrombocytopenic patients.