The synthetic peptide P-197 inhibits human T-cell leukemia virus type 1 envelope-mediated syncytium formation by a mechanism that is independent of Hsc70.
Entry of human T-cell leukemia virus type 1 (HTLV-1) into cells is mediated by the viral envelope glycoproteins gp46 and gp21. The gp46 surface glycoprotein binds to a poorly characterized cell surface receptor, thereby promoting the gp21-dependent fusion of the viral and cellular membranes. Interestingly, a synthetic peptide (P-197) simulating amino acids 197 to 216 of gp46 strongly inhibits envelope-dependent membrane fusion with Molt-4 target cells. It has been suggested that this peptide acts by competitively binding to Hsc70, a putative cellular receptor for HTLV-1. We now demonstrate that P-197 inhibits membrane fusion among diverse HTLV-1-permissive target cells. Importantly, most of these cells lack detectable levels of Hsc70, indicating that P-197 inhibits membrane fusion by a mechanism that is Hsc70 independent. We now suggest that competition for primary receptor binding is unlikely to account for the inhibitory activity of P-197. Understanding the mechanism by which P-197 functions may reveal concepts of general relevance to antiretroviral chemotherapy.
Brighty
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DW
Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK.
Jassal
S R
SR
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D015686:Gene Products, env / Q000494:pharmacology*; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology*; D006367:HeLa Cells; D015368:Human T-lymphotropic virus 1 / Q000187:drug effects*; D006801:Humans; D008561:Membrane Fusion / Q000187:drug effects*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology*; D015682:Retroviridae Proteins, Oncogenic / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D015686:Gene Products, env; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C494371:HSPA8 protein, human; D010446:Peptide Fragments; D015682:Retroviridae Proteins, Oncogenic; C055266:gp46 protein, Human T-cell leukemia virus type I