Antibody against integrin lymphocyte function-associated antigen 1 inhibits HIV type 1 infection in primary cells through caspase-8-mediated apoptosis

Tiffany N. Walker, Lisa M. Cimakasky, Ebony M. Coleman, M. Nia Madison, James Hildreth

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

HIV-1 infection induces formation of a virological synapse wherein CD4, chemokine receptors, and cell-adhesion molecules such as lymphocyte function-associated antigen 1 (LFA-1) form localized domains on the cell surface. Studies show that LFA-1 on the surface of HIV-1 particles retains its adhesion function and enhances virus attachment to susceptible cells by binding its counterreceptor intercellular adhesion molecule 1 (ICAM-1). This virus-cell interaction augments virus infectivity by facilitating binding and entry events. In this study, we demonstrate that inhibition of the LFA-1/ICAM-1 interaction by a monoclonal antibody leads to decreased virus production and spread in association with increased apoptosis of HIV-infected primary T cells. The data indicate that the LFA-1/ICAM-1 interaction may limit apoptosis in HIV-1-infected T cells. This phenomenon appears similar to anoikis wherein epithelial cells are protected from apoptosis conferred by ligand-bound integrins. These results have implications for further understanding HIV pathogenesis and replication in peripheral compartments and lymphoid organs.

Original languageEnglish (US)
Pages (from-to)371-383
Number of pages13
JournalAIDS Research and Human Retroviruses
Volume29
Issue number2
DOIs
StatePublished - Feb 1 2013

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Infectious Diseases

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