The α-helical (AH) peptide derived from the hepatitis C virus can discriminate between membrane compositions to kill some cholesterol-containing viruses while leaving host cells unharmed, suggests recent data published in Biophysical Journal.

Prior research has shown that the AH peptide has antiviral properties, which help the peptide use host cell structures for hepatitis C virus (HCV) replication. This process also exposes viral membranes that allow enzymes to destroy pathogens. In this study, researchers from the Nanyang Technological University in Singapore examined why the AH peptide attacks viral envelopes but does not harm the host cell membranes.

The researchers tested AH peptide on different model lipid membranes that varied by size and chemical composition. They added the AH peptide to a population of giant unilamellar vesicles (GUVs) with cholesterol-rich membranes and noted a change in the membrane molecular organization and a redistribution of phase-sensitive fluorophore.


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The researchers incubated the single fluid-phase lipid POPC with the AH peptide at comparable concentrations (1 to 5 µm), and found no perturbations of the membrane boundary.  When the peptide concentration was increased to 10 to 25 µm, however, there was a significant deformation of the membrane.

Additional experiments suggested that the AH peptide discriminates between membrane compositions. 

“Because the membranes of viruses inhibited by the AH peptide are invariably enriched in raft-forming [cholesterol] and [sphingomyelin] and possess intrinsic positive curvatures, we infer that the broad-spectrum virocidal properties of the AH peptide stem from its ability to preferentially bind and destabilize the viron due to the combined effects of size and composition,” the authors wrote in the study.

The study investigators plan to continue their research with additional membrane compositions, and examine the interplay of viral peptides with membranes.

Reference

1. Hanson JM, Gettel DL, Tabaei SR, et al. Cholesterol-Enriched Domain Formation Induced by Viral-Encoded, Membrane-Active Amphipathic Peptide. Biophys J.  2016; 110:176-187. doi: 10.1016/j.bpj.2015.11.032.