3 years ago

Effects of HIV-1 gp41-Derived Virucidal Peptides on Virus-like Lipid Membranes

Effects of HIV-1 gp41-Derived Virucidal Peptides on Virus-like Lipid Membranes
Beatriz Apellaniz, Jesús Pérez-Gil, Nerea Huarte, José Requejo-Isidro, Antonio Cruz, Johanna Torralba, José L. Nieva, Itziar R. Oar-Arteta, Itziar Martin-Ugarte, Pablo Carravilla

Abstract

Membrane fusion induced by the envelope glycoprotein enables the intracellular replication of HIV-1; hence, this process constitutes a major target for antiretroviral compounds. It has been proposed that peptides having propensity to interact with membrane interfaces might exert broad antiviral activity against enveloped viruses. To test this hypothesis, in this contribution we have analyzed the antiviral effects of peptides derived from the membrane-proximal external region and the transmembrane domain of the envelope glycoprotein subunit gp41, which display different degrees of interfacial hydrophobicity. Our data support the virucidal activity of a region that combines hydrophobic-at-interface membrane-proximal external region aromatics with hydrophobic residues of the transmembrane domain, and contains the absolutely conserved 679LWYIK/R683 sequence, proposed to embody a "cholesterol recognition/interaction amino acid consensus" motif. We further sought to correlate the antiviral activity of these peptides and their effects on membranes that mimic lipid composition and biophysical properties of the viral envelope. The data revealed that peptides endowed with virucidal activity were membrane active and induced permeabilization and fusion of virus-like lipid vesicles. In addition, they modulated lipid packing and miscibility of laterally segregated liquid domains, two properties that depend on the high cholesterol content of the viral membrane. Thus, the overall experimental evidence is consistent with a pattern of HIV inhibition that involves direct alteration of the physical chemistry of the virus membrane. Furthermore, the sequence-dependent effects observed might guide the development of new virucidal peptides.

Publisher URL: http://www.cell.com/biophysj/fulltext/S0006-3495(17)30747-6

DOI: 10.1016/j.bpj.2017.06.061

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