Synthetic peptide analogs of intercellular adhesion molecule 1 (ICAM-1) inhibit HIV-1 replication in MT-2 cells.
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 micrograms/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. 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 micrograms/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
Fecondo
J V
JV
Cellular Immunology Unit, Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Pavuk
N C
NC
Silburn
K A
KA
Read
D M
DM
Mansell
A S
AS
Boyd
A W
AW
McPhee
D A
DA
D000595:Amino Acid Sequence; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000494:pharmacology*; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D015726:Giant Cells / Q000473:pathology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D016169:Lymphocyte Function-Associated Antigen-1 / Q000187:drug effects; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D010446:Peptide Fragments; D018799:Intercellular Adhesion Molecule-1