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Article Dans Une Revue Biochimica et Biophysica Acta:Biomembranes Année : 2019

Studies of membranotropic and fusogenic activity of two putative HCV fusion peptides

Résumé

Over the past decades, membranotropic peptides such as positively charged cell-penetrating peptides (CPPs) or amphipathic antimicrobial peptides (AMPs) have received increasing interest in order to improve therapeutic agent cellular uptake. As far as we are concerned, we were interested in studying HCV fusion peptides as putative anchors. Two peptides, HCV6 and HCV7, were identified and conjugated to a fluorescent tag NBD and tested for their interaction with liposomes as model membranes. DSC and spectrofluorescence analyses demonstrate HCV7 propensity to insert or internalize in vesicles containing anionic lipids DMPG whereas no activity was observed with zwitterionic DMPC. This behavior could be explained by the peptide sequence containing a cationic arginine residue. On the contrary, HCV6 did not exhibit any membranotropic activity but was the only sequence able to induce liposomes' fusion or aggregation monitored by spectrofluorescence and DLS. This two peptides mild activity was related to their inefficient structuration in contact with membrane mimetics, which was demonstrated by CD and NMR experiments. Altogether, our data allowed us to identify two promising membrane-active peptides from E1 and E2 HCV viral proteins, one fusogenic (HCV6) and the other membranotropic (HCV7). The latter was also confirmed by fluorescence microscopy with CHO cells, indicating that HCV7 could cross the plasma membrane via an endocytosis process. Therefore, this study provides new evidences supporting the identification of HCV6 as the HCV fusion peptide as well as insights on a novel membranotropic peptide from the HCV-E2 viral protein.
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Dates et versions

hal-01920493 , version 1 (13-11-2018)

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Simon Gonzalez, Florian Gallier, Sabrina Kellouche, Franck Carreiras, Ettore Novellino, et al.. Studies of membranotropic and fusogenic activity of two putative HCV fusion peptides. Biochimica et Biophysica Acta:Biomembranes, 2019, 1861 (1), pp.50-61. ⟨10.1016/j.bbamem.2018.10.011⟩. ⟨hal-01920493⟩
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