Analysis of synthetic peptides from heptad-repeat domains of herpes simplex virus type 1 glycoproteins H and B.
Human herpesviruses enter cells by fusion of their own membrane with a cellular membrane through the concerted action of multiple viral proteins and cellular receptors. Two conserved viral glycoproteins, gB and gH, are required for herpes simplex virus type 1 (HSV-1)-mediated membrane fusion, but little is known of how these proteins cooperate during entry. Both glycoproteins were shown to contain heptad repeat (HR) sequences predicted to form alpha-helical coiled coils, and the inhibitory activity against infection of four sets of synthetic peptides corresponding to HR1 and HR2 of gB and gH was tested. The interactions between these HR peptides were also investigated by circular dichroism, native polyacrylamide-gel electrophoresis and size exclusion high-performance liquid chromatography. gH coiled-coil peptides were more effective than gB coiled-coils peptides in inhibiting virus infectivity. The peptides did not impair fusion when added to cells immediately after infection. In contrast, inhibition of infection was observed, albeit to various extents, when peptides were added to virus before or during inoculation. The results of biophysical analyses were indicative of the existence of an interaction between HR1 and HR2 of gH and suggest that the HRs of gB and gH do not interact with each other.
Galdiero
Stefania
S
Istituto di Biostrutture e Bioimmagini, CNR, Via Mezzocannone 16, 80134 Naples, Italy.|Centro Interuniversitario di Ricerca sui Peptidi Bioattivi, University of Naples Federico II, Via Mezzocannone 16, 80134 Naples, Italy.|Department of Biological Sciences, Division of Biostructures, University of Naples Federico II, Via Mezzocannone 16, 80134 Naples, Italy.
Vitiello
Mariateresa
M
Department of Experimental Medicine, II University of Naples, Via De Crecchio 7, 80138 Naples, Italy.|Centro Interuniversitario di Ricerca sui Peptidi Bioattivi, University of Naples Federico II, Via Mezzocannone 16, 80134 Naples, Italy.
D'Isanto
Marina
M
Department of Experimental Medicine, II University of Naples, Via De Crecchio 7, 80138 Naples, Italy.
Falanga
Annarita
A
Department of Experimental Medicine, II University of Naples, Via De Crecchio 7, 80138 Naples, Italy.
Collins
Craig
C
Division of Virology, Department of Pathology, University of Cambridge, Cambridge, UK.
Raieta
Katia
K
Department of Experimental Medicine, II University of Naples, Via De Crecchio 7, 80138 Naples, Italy.
Pedone
Carlo
C
Istituto di Biostrutture e Bioimmagini, CNR, Via Mezzocannone 16, 80134 Naples, Italy.|Centro Interuniversitario di Ricerca sui Peptidi Bioattivi, University of Naples Federico II, Via Mezzocannone 16, 80134 Naples, Italy.|Department of Biological Sciences, Division of Biostructures, University of Naples Federico II, Via Mezzocannone 16, 80134 Naples, Italy.
Browne
Helena
H
Division of Virology, Department of Pathology, University of Cambridge, Cambridge, UK.
Galdiero
Massimiliano
M
Department of Experimental Medicine, II University of Naples, Via De Crecchio 7, 80138 Naples, Italy.|Centro Interuniversitario di Ricerca sui Peptidi Bioattivi, University of Naples Federico II, Via Mezzocannone 16, 80134 Naples, Italy.
D000595:Amino Acid Sequence; D000818:Animals; D002459:Cell Fusion; D002522:Chlorocebus aethiops; D006561:Herpes Simplex / Q000821:virology; D008561:Membrane Fusion; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000235:genetics / Q000494:pharmacology*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary / Q000235:genetics; D018139:Simplexvirus / Q000737:chemistry* / Q000187:drug effects* / Q000502:physiology; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000235:genetics; D014779:Virus Replication / Q000187:drug effects
D010455:Peptides; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus; C044200:glycoprotein H, herpes simplex virus type 1