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Role of LFA‐1 in the transmission and pathogenesis of human immunodeficiency virus type 1 (HIV‐1)
Author(s) -
Walker Tiffany Nicole,
Hildreth James EK
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.537.1
Subject(s) - monoclonal antibody , syncytium , apoptosis , biology , lymphocyte function associated antigen 1 , virology , virus , antibody , programmed cell death , immunology , microbiology and biotechnology , biochemistry
HIV‐1infection induces formation of a virological synapse wherein CD4, chemokine receptors, and cell adhesion moleculessuch as the integrin LFA‐1 [RNSB1]form localized domains on the cell surface. Previous studies have shown that LFA‐1 on the surface of HIV‐1 particlesnot only retains its cellular function but also enhances virus attachment to susceptible cells by binding its counterreceptor ICAM‐1. Findings from our laboratory revealed that monoclonal antibodies (Mab) specific for LFA‐1 blocked HIV‐1 mediated syncytia formationand enhanced neutralization by antibodies from AIDS patients and by gp120 Mabs. The objective of this study is to determine if LFA‐1/ICAM‐1 interaction plays a limiting role in apoptosis, a process linked to both HIV‐1 infection and integrin biology such that disruption of this interaction leads to increasedapoptosis in HIV‐1‐infected cells. Using the TUNEL assay, we observed increased cell death in HIV‐1‐infected primary T cells treated with anti‐LFA‐1 Mab[RNSB2], as well as increased caspase 8 activation. HIV‐1‐infected cells treated with anti‐LFA‐1 Mab also released less virus compared to HIV‐1‐infected cells alone. These results suggests that anti‐LFA‐1 Mab blocks HIV‐1 infection by inducing apoptosis and that LFA‐1‐mediated signaling may be necessary to prevent HIV‐1‐induced apoptosis, thereby contributing to the spread of infection. Supported by NIH (R01HD040772)