title: 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.
abstract: The carboxy-terminal 29 amino acids of the human immunodeficiency virus type 1 transmembrane glycoprotein (HIV-1 TM) are referred to as lentivirus lytic peptide 1 (LLP-1). Synthetic peptides corresponding to LLP-1 have been shown to induce cytolysis and to alter the permeability of cultured cells to various small molecules. To address the mechanisms by which LLP-1 induces cytolysis and membrane permeability changes, various concentrations of LLP-1 were incubated with Xenopus laevis oocytes, and two-electrode, voltage-clamp recording measurements were performed. LLP-1 at concentrations of 75 nM and above induced dramatic alterations in the resting membrane potential and ionic permeability of Xenopus oocytes. These concentrations of LLP-1 appeared to induce a major disruption of plasma membrane electrophysiological integrity. In contrast, concentrations of LLP-1 of 20-50 nM induced changes in membrane ionic permeability that mimic changes induced by compounds, such as the bee venom peptide melittin, that are known to form channel-like structures in biological membranes at sublytic concentrations. An analog 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 contribute to cytolysis of HIV-1-infected CD4+ cells.
authors.affiliation: Graduate Program in Molecular and Cellular Biology, Tulane University, New Orleans, Louisiana 70112, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Comardelle
authors.forename: C H
authors.initials: CH
authors.lastname: Norris
authors.forename: D R
authors.initials: DR
authors.lastname: Plymale
authors.forename: P J
authors.initials: PJ
authors.lastname: Gatti
authors.forename: B
authors.initials: B
authors.lastname: Choi
authors.forename: C D
authors.initials: CD
authors.lastname: Fermin
authors.forename: A M
authors.initials: AM
authors.lastname: Haislip
authors.forename: S B
authors.initials: SB
authors.lastname: Tencza
authors.forename: T A
authors.initials: TA
authors.lastname: Mietzner
authors.forename: R C
authors.initials: RC
authors.lastname: Montelaro
authors.forename: R F
authors.initials: RF
authors.lastname: Garry
mesh_terms: D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects*; D015700:HIV Envelope Protein gp41 / Q000737:chemistry*; D017136:Ion Transport; D009865:Oocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000494:pharmacology*; D014982:Xenopus laevis
chemical_list: D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments