Evidence for a role of the membrane-proximal region of herpes simplex virus type 1 glycoprotein H in membrane fusion and virus inhibition.
We have identified a putative membrane-interacting domain preceding the transmembrane domain of the Herpes simplex virus type 1 (HSV-1) glycoprotein H (gH). Peptides derived from this region interact strongly with membranes and show a high tendency to partition at the interface. This region is predicted to bind at the membrane interface by adopting an alpha helical structure. Peptides representing either the HSV-1 gH pretransmembrane region or a scrambled control with a different hydrophobic profile at the point of interface have been studied. The peptides derived from this domain of gH induce the fusion of liposomal membranes, adopt helical conformations in membrane mimetic environments and are able to inhibit HSV-1 infectivity. The pretransmembrane region appears to be a common feature in viral fusion proteins of several virus families, and such a feature might be related to their fusogenic function. The identification of membrane-interacting regions capable of modifying the biophysical properties of phospholipid membranes lends weight to the view that such domains might function directly in the fusion process and could facilitate the future development of HSV-1 entry inhibitors.
Galdiero
Stefania
S
Department of Biological Sciences, Division of Biostructures, University of Naples Federico II, Via Mezzocannone 16, Napoli, Italy.
Falanga
Annarita
A
Vitiello
Mariateresa
M
D'Isanto
Marina
M
Collins
Craig
C
Orrei
Veronica
V
Browne
Helena
H
Pedone
Carlo
C
Galdiero
Massimiliano
M
D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000737:chemistry / Q000502:physiology; D057927:Hydrophobic and Hydrophilic Interactions; D008055:Lipids / Q000737:chemistry; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D018139:Simplexvirus / Q000737:chemistry* / Q000187:drug effects; D014759:Viral Envelope Proteins / Q000737:chemistry*; D053586:Virus Internalization
D008055:Lipids; D010446:Peptide Fragments; D014759:Viral Envelope Proteins; C044200:glycoprotein H, herpes simplex virus type 1