       Document 0849
 DOCN  M9640849
 TI    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.
 DT    9604
 AU    Zauli G; Catani L; Gibellini D; Re MC; Milani D; Borgatti P; Bassini A;
       La Placa M; Capitani S; Institute of Human Anatomy, University of
       Ferrara, Italy.
 SO    Br J Haematol. 1995 Oct;91(2):290-8. Unique Identifier : AIDSLINE
       MED/96027647
 AB    We investigated whether cells belonging to the megakaryocytic 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 (> 50%) and were
       efficiently infected with HIV-1, as judged by the presence of proviral
       DNA after polymerase chain reaction analysis and by quantitative
       evaluation of gag p24 antigen in the culture supernatants. Of note,
       infection with HIV-1 in both primary BM megakaryocytes and HEL cells was
       specifically blocked by soluble recombinant CD4. To ascertain whether
       the CD4 receptor was essential for infection of megakaryocytic cells,
       HEL were subcloned into CD4+ 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 gp120 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.
 DE    Antigens, CD4/*PHYSIOLOGY  Apoptosis/*PHYSIOLOGY  Bone
       Marrow/PATHOLOGY/VIROLOGY  Cell Line  Cell Survival  Electrophoresis,
       Agar Gel  Flow Cytometry  Human  HIV Infections/*IMMUNOLOGY  *HIV-1
       Megakaryocytes/PATHOLOGY/*VIROLOGY  Support, Non-U.S. Gov't  JOURNAL
       ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
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