The identification and characterization of fusogenic domains in herpes virus glycoprotein B molecules.
The molecular mechanism of entry of herpes viruses requires a multicomponent fusion system. Virus entry and cell-cell fusion of Herpes simplex virus (HSV) requires four glycoproteins: gD, gB and gH/gL. The role of gB remained elusive until recently, when the crystal structure of HSV-1 gB became available. Glycoprotein B homologues represent the most highly conserved group of herpes virus glycoproteins; however, despite the high degree of sequence and structural conservation, differences in post-translational processing are observed for different members of this virus family. Whereas gB of HSV is not proteolytically processed after oligomerization, most other gB homologues are cleaved by a cellular protease into subunits that remain linked through disulfide bonds. Proteolytic cleavage is common for activation of many other viral fusion proteins, so it remains difficult to envisage a common role for different herpes virus gB structures in the fusion mechanism. We selected bovine herpes virus type 1 (BoHV-1) and herpes simplex virus type 1 (HSV-1) as representative viruses expressing cleaved and uncleaved gBs, and have screened their amino acid sequences for regions of highly interfacial hydrophobicity. Synthetic peptides corresponding to such regions were tested for their ability to induce the fusion of large unilamellar vesicles and to inhibit herpes virus infection. These results underline that several regions of the gB protein are involved in the mechanism of membrane interaction.
Galdiero
Stefania
S
Department of Biological Sciences, Division of Biostructures, University of Naples Federico II, Via Mezzocannone 16, 80134 Napoli, Italy.
Vitiello
Mariateresa
M
D'Isanto
Marina
M
Falanga
Annarita
A
Cantisani
Marco
M
Browne
Helena
H
Pedone
Carlo
C
Galdiero
Massimiliano
M
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D002460:Cell Line; D002522:Chlorocebus aethiops; D007242:Herpesvirus 1, Bovine / Q000737:chemistry / Q000187:drug effects; D018259:Herpesvirus 1, Human / Q000187:drug effects; D057927:Hydrophobic and Hydrophilic Interactions; D008561:Membrane Fusion; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000737:chemistry*; D014760:Viral Fusion Proteins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D010446:Peptide Fragments; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins; C040495:glycoprotein B, Simplexvirus