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

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Carravilla, Pablo and Cruz Rodríguez, Antonio and Martín-Ugarte, Itziar and Oar-Arteta, Itziar R. and Torralba, Johanna and Apellaniz, Beatriz and Pérez Gil, Jesús and Requejo Isidro, José and Huarte, Nerea and Nieva, José L. (2017) Effects of HIV-1 gp41-Derived Virucidal Peptides on Virus-like Lipid Membranes. Biophysical Journal, 113 (6). pp. 1301-1310. ISSN 0006-3495, ESSN: 1542-0086

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



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.


Item Type:Article
Uncontrolled Keywords:Pepetides; Lipid Membranes; HIV
Subjects:Medical sciences > Biology > Biochemistry
ID Code:46498
Deposited On:19 Feb 2018 09:29
Last Modified:19 Feb 2018 11:38

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