Fusogenic domains in herpes simplex virus type 1 glycoprotein H.
Infection of eukaryotic cells by enveloped viruses requires fusion between the viral envelope and the cellular plasma or endosomal membrane. The actual merging of the two membranes is mediated by viral envelope glycoproteins, which generally contain a highly hydrophobic region termed the fusion peptide. The entry of herpesviruses is mediated by three conserved proteins: glycoproteins B, H (gH), and L. However, how fusion is executed remains unknown. Herpes simplex virus type 1 gH exhibits features typical of viral fusion glycoproteins, and its ectodomain seems to contain a putative internal fusion peptide. Here, we have identified additional internal segments able to interact with membranes and to induce membrane fusion of large unilamellar vesicles. We have applied the hydrophobicity-at-interface scale proposed by Wimley and White (Wimley, W. C., and White, S. H. (1996) Nat. Struct. Biol. 3, 842-848) to identify six hydrophobic stretches within gH with a tendency to partition into the membrane interface, and four of them were able to induce membrane fusion. Experiments in which equimolar mixtures of gH peptides were used indicated that different fusogenic regions may act in a synergistic way. The functional and structural characterization of these segments suggests that herpes simplex virus type 1 gH possesses several fusogenic internal peptides that could participate in the actual fusion event.
Galdiero
Stefania
S
Department of Biological Sciences, Division of Biostructures, University of Naples "Federico II", Naples, Italy.
Falanga
Annarita
A
Vitiello
Mariateresa
M
Browne
Helena
H
Pedone
Carlo
C
Galdiero
Massimiliano
M
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D018259:Herpesvirus 1, Human / Q000378:metabolism*; D008561:Membrane Fusion; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D020543:Proteome; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014759:Viral Envelope Proteins / Q000737:chemistry*
D010446:Peptide Fragments; D020543:Proteome; D014759:Viral Envelope Proteins; C044200:glycoprotein H, herpes simplex virus type 1