SYNTHETIC PEPTIDE ANALOGS OF INTERCELLULAR-ADHESION MOLECULE-1 (ICAM-1) INHIBIT HIV-1 REPLICATION IN MT-2 CELLS

FECONDO, JV; PAVUK, NC; SILBURN, KA; READ, DMY; MANSELL, AS; Boyd, AW; MCPHEE, DA

Author(s): FECONDO, JV; PAVUK, NC; SILBURN, KA; READ, DMY; MANSELL, AS; Boyd, AW; MCPHEE, DA;
Details: Publication Year 1993-08,Volume 9,Issue #8,Page 733-740
Journal Title: AIDS RESEARCH AND HUMAN RETROVIRUSES
Publication Type: Journal Article
Abstract: On the basis of reports demonstrating possible roles for leukocyte function-associated antigen 1 (LFA-1) and intercellular adhesion molecule 1 (ICAM-1), the ligand for LFA-1, in human immunodeficiency virus type 1 (HIV-1) infection, we have explored the involvement of the ICAM-1 molecule by using selected synthetic peptides derived from the protein sequence. Replication was assessed in MT-2 cells, highly susceptible to HIV infection, in the presence of four synthetic peptides derived from the ICAM-1 amino acid sequence. This cell type was chosen for the ability to form marked syncytia on infection with cell-free virus. Under the conditions used, minimal or no cytotoxicity was observed with the peptides up to concentrations of 50 mug/ml. A peptide corresponding to a unique region of ICAM-1, JF9 [ICAM-1(367-394, A-378)], had little effect on virus replication despite its ability to inhibit cell-cell adhesion.1 In contrast, an N-terminal peptide, JF7B [ICAM-1(1-23)], consistently inhibited virus replication in MT-2 cells in a dose-dependent manner, as measured by cell-free reverse transcriptase (RT) activity (up to 70% inhibition), soluble virus antigen production (up to 60% inhibition), and syncytium formation (virtually complete inhibition up to 6 days post infection). Testing of W-CAM-1 antibody, and anti-ICAM-1 antibody that inhibits cell-cell adhesion, revealed no significant inhibitory effects on RT activity, virus antigen production, and syncytium formation in HIV-1-infected MT-2 cells at a level that markedly inhibited cell-cell adhesion (10 mug/ml). These preliminary results suggest a possible role for ICAM-1 in HIV-1 infection, particularly in syncytium formation, and that the functional region of ICAM-1 involved in this process is separate from the previously identified sites of the molecule involved in cell-cell adhesion through interaction with LFA-1.
Publisher: MARY ANN LIEBERT INC PUBL
Keywords: HUMAN-IMMUNODEFICIENCY-VIRUS; BINDING-SITE; T-CELLS; ENVELOPE GLYCOPROTEIN; SYNCYTIUM FORMATION; ENDOTHELIAL-CELLS; ANTIGEN-1 LFA-1; LYMPHOCYTES-T; HTLV-III/LAV; CD4 PROTEIN
Publisher's Version: https://doi.org/10.1089/aid.1993.9.733
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 1993-08-01 12:00:00