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1996-03-04
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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
protected by Copyright Law (Title 17, U.S.Code).