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Synthetic peptide analogs of intercellular adhesion molecule 1 (ICAM-1) inhibit HIV-1 replication in MT-2 cells
J V Fecondo1, N C Pavuk, K A Silburn
1Cellular Immunology Unit, Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Insights
Synthetic peptides targeting intercellular adhesion molecule 1 (ICAM-1) were tested for human immunodeficiency virus type 1 (HIV-1) inhibition. An N-terminal ICAM-1 peptide significantly inhibited HIV-1 replication and syncytium formation in MT-2 cells.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Leukocyte function-associated antigen 1 (LFA-1) and its ligand, intercellular adhesion molecule 1 (ICAM-1), are implicated in human immunodeficiency virus type 1 (HIV-1) infection.
- Investigating the role of ICAM-1 in HIV-1 pathogenesis is crucial for developing novel therapeutic strategies.
Purpose of the Study:
- To explore the involvement of ICAM-1 in HIV-1 replication using synthetic peptides derived from its amino acid sequence.
- To assess the inhibitory potential of ICAM-1-derived peptides on HIV-1 replication in MT-2 cells.
Main Methods:
- Four synthetic peptides from the ICAM-1 sequence were tested for their effects on HIV-1 replication in MT-2 cells.
- Viral replication was measured by reverse transcriptase (RT) activity, soluble virus antigen production, and syncytium formation.
- Cytotoxicity of peptides and inhibitory effects of an anti-ICAM-1 antibody (W-CAM-1) were also evaluated.
Main Results:
- A peptide from a unique ICAM-1 region (JF9) showed minimal effect on viral replication despite inhibiting cell-cell adhesion.
- An N-terminal ICAM-1 peptide (JF7B) demonstrated dose-dependent inhibition of HIV-1 replication, reducing RT activity by up to 70% and antigen production by up to 60%.
- JF7B peptide virtually abolished syncytium formation, while W-CAM-1 antibody had no significant effect on viral replication markers.
Conclusions:
- The N-terminal region of ICAM-1, represented by peptide JF7B, plays a significant role in HIV-1 replication.
- Targeting this ICAM-1 region with specific peptides may represent a potential therapeutic approach for HIV-1 infection.
- ICAM-1's role in HIV-1 infection is complex and peptide-specific, distinct from its function in cell adhesion mediated by antibodies.
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 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)