A SYNTHETIC PEPTIDE CORRESPONDING TO THE CARBOXY-TERMINUS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 TRANSMEMBRANE GLYCOPROTEIN INDUCES ALTERATIONS IN THE IONIC PERMEABILITY OF XENOPUS-LAEVIS OOCYTES

The carboxy-terminal 29 amino acids of the human immunodeficiency viru s type 1 transmembrane glycoprotein (HIV-1 TM) are referred to as lent ivirus lytic peptide 1 (LLP-1), Synthetic peptides corresponding to LL P-1 have been shown to induce cytolysis and to alter the permeability of cultured cells to various small molecules, To address the mechanism s by which LLP-1 induces cytolysis and membrane permeability changes, various concentrations of LLP-1 mere incubated with Xenopus laevis ooc ytes, and two-electrode, voltage-clamp recording measurements were per formed, LLP-1 at concentrations of 75 nM and above induced dramatic al terations in the resting membrane potential and ionic permeability of Xenopus oocytes, These concentrations of LLP-1 appeared to induce a ma jor disruption of plasma membrane electrophysiological integrity. In c ontrast, concentrations of LLP-1 of 20-50 nM induced changes in membra ne ionic permeability that mimic changes induced by compounds, such as the bee venom peptide melittin, that are known to form channel-like s tructures in biological membranes at sublytic concentrations, An analo g of LLP-1 with greatly reduced cytolytic activity failed to alter the electrophysiological properties of Xenopus oocytes, Thus, by altering plasma membrane ionic permeability, the carboxy terminus of TM may co ntribute to cytolysis of HIV-l-infected CD4(+) cells.