Role of membranotropic sequences from herpes simplex virus type I glycoproteins B and H in the fusion process.
The entry of enveloped viruses involves attachment followed by close apposition of the viral and plasma membranes. Then, either on the cell surface or in an endocytotic vesicle, the two membranes fuse by an energetically unfavourable process requiring the destabilisation of membrane microenvironment in order to release the viral nucleocapsid into the cytoplasm. The core fusion machinery, conserved throughout the herpesvirus family, involves glycoprotein B (gB) and the non-covalently associated complex of glycoproteins H and L (gH/gL). Both gB and gH possess several hydrophobic domains necessary for efficient induction of fusion, and synthetic peptides corresponding to these regions are able to associate to membranes and induce fusion of artificial liposomes. Here, we describe the first application of surface plasmon resonance (SPR) to the study of the interaction of viral membranotropic peptides with model membranes in order to enhance our molecular understanding of the mechanism of membrane fusion. SPR spectroscopy data are supported by tryptophan fluorescence, circular dichroism and electron spin resonance spectroscopy (ESR). We selected peptides from gB and gH and also analysed the behaviour of HIV gp41 fusion peptide and the cationic antimicrobial peptide melittin. The combined results of SPR and ESR showed a marked difference between the mode of action of the HSV peptides and the HIV fusion peptide compared to melittin, suggesting that viral-derived membrane interacting peptides all act via a similar mechanism, which is substantially different from that of the non-cell selective lytic peptide melittin.
Galdiero
Stefania
S
Department of Biological Sciences, Division of Biostructures - University of Naples Federico II, Via Mezzocannone 16, 80134, Napoli, Italy.
Falanga
Annarita
A
Vitiello
Giuseppe
G
Vitiello
Mariateresa
M
Pedone
Carlo
C
D'Errico
Gerardino
G
Galdiero
Massimiliano
M
D000595:Amino Acid Sequence; D002021:Buffers; D002784:Cholesterol / Q000378:metabolism; D002942:Circular Dichroism; D018259:Herpesvirus 1, Human / Q000378:metabolism*; D007536:Isomerism; D007700:Kinetics; D008051:Lipid Bilayers / Q000378:metabolism; D008561:Membrane Fusion; D008956:Models, Chemical; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D017433:Protein Structure, Secondary; D013050:Spectrometry, Fluorescence; D013113:Spin Labels; D020349:Surface Plasmon Resonance; D014364:Tryptophan / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000378:metabolism*
D002021:Buffers; D008051:Lipid Bilayers; D010455:Peptides; D010713:Phosphatidylcholines; D013113:Spin Labels; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus; C044200:glycoprotein H, herpes simplex virus type 1; D014364:Tryptophan; D002784:Cholesterol