The membrane-active regions of the dengue virus proteins C and E

Abstract

We have identified the membranotropic regions of proteins C and E of DENV virus by performing an exhaustive study of membrane rupture induced by two C and E-derived peptide libraries on model membranes having different phospholipid compositions as well as its ability to modulate the DEPE L(β)-L(α) and L(α)-H(II) phospholipid phase transitions. Protein C presents one hydrophobic leakage-prone region coincidental with a proposed membrane interacting domain, whereas protein E presents five membrane-rupture zones coincidental with different significant zones of the protein, i.e., the fusion peptide, a proline-rich sequence, a sequence containing a hydrophobic pocket as well as the stem and transmembrane domains of the protein. The identification of these membrane-active segments supports their role in viral membrane fusion, formation of the replication complex and morphogenesis and therefore attractive targets for development of new anti-viral compounds.

Release of Dengue Virus Genome Induced by a Peptide Inhibitor

“…The observed peptide-lipid membrane interactions are not merely charge based, as binding and disruption occurred with both zwitterionic POPC vesicles as well as negatively-charged 9∶1 POPC/POPG vesicles. Supporting these observations, a recent study of the membrane disruption ability of overlapping peptides from dengue virus type 2 C and E proteins showed that E protein stem derived peptides were highly disruptive to liposomes prepared with a wide variety of lipid compositions [19].…”

“…The lack of apparent disruption of cellular plasma membranes and other viral membranes may be due to lipid composition, protein incorporation, or active repair of cellular membranes. Dengue virus particles bud from internal endoplasmic reticulum membranes of infected cells and so likely have a different composition from the plasma membrane, although the membrane disruption activity of stem region peptides is not strongly influenced by lipid membrane composition [19].…”

N-Terminal AH2 segment of protein NS4B from hepatitis C virus. Binding to and interaction with model biomembranes

“…We have recently identified the membrane-active regions of a number of viral proteins by observing the effect of peptide libraries on model membrane integrity, including HCV NS4B [19][20][21][22][23]. These results allowed us to propose the location of different segments in these proteins that should be implicated in protein-lipid and protein-protein interactions.…”

gH625: A milestone in understanding the many roles of membranotropic peptides

“…Particular attention has also been devoted to the effect of additional membranotropic sequences on the overall fusogenicity. The presence of additional fusogenic sequences was evidenced in Sendai F1 [34], Measles F1 [35], SARS-CoV S2 [36], Hepatitic C virus E1 and E2 [37], Dengue E [38,39] and Herpes Virus gB and gH [40][41][42]. The idea that a single fusion peptide is the solely responsible for the complete membrane fusion event has been substituted by the assumption that a concerted action of different membranotropic regions is necessary for membrane interacting/perturbing activity.…”