| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, U.K.
Four monoclonal antibodies to glycoprotein D (gD) of herpes simplex virus (HSV) types 1 and 2 neutralized virus in the presence of complement but exhibited diverse activities in its absence. Amino acid substitutions that conferred resistance to neutralization by each antibody were identified by deriving the nucleotide sequence of the gD gene from resistant mutants. Each antibody selected a substitution from different parts of the molecule and mutants resistant to a single antibody always arose from the same mutation. One of the antibodies reacted with a synthetic oligopeptide corresponding to the region of the molecule in which amino acid substitution conferred resistance, but the remaining three antibodies failed to react with predicted oligopeptide targets. These antibodies may therefore react with ‘discontinuous’ epitopes, a view supported by the observation that two of these three antibodies competed with each other in binding assays despite the fact that substitutions conferring resistance to neutralization arose nearly 100 residues apart in the primary sequence. The four antibodies had very different biological properties. One antibody neutralized infectivity but did not inhibit cell fusion, one antibody inhibited cell fusion but did not neutralize, while a third antibody had both activities. One antibody had neither activity but enhanced the infectivity of HSV-2 in a type-specific manner. The ability of antibodies to inhibit cell fusion by syncytial virus strains correlated with an ability to prevent plaque enlargement by a non-syncytial virus strain, implying a role for gD in the intercellular spread of virus that is independent of the syncytial phenotype. We found no correlation between neutralizing activity and anti-fusion activity suggesting that, while gD is involved in cell fusion, it has at least one other function which is required for infectivity.
Keywords: HSV, glycoprotein D, monoclonal antibodies, resistance
Received 27 November 1985;
accepted 27 February 1986.
This article has been cited by other articles:
|
|
 |
|
  E. Lazear, A. Carfi, J. C. Whitbeck, T. M. Cairns, C. Krummenacher, G. H. Cohen, and R. J. Eisenberg Engineered Disulfide Bonds in Herpes Simplex Virus Type 1 gD Separate Receptor Binding from Fusion Initiation and Viral Entry J. Virol., January 15, 2008; 82(2): 700 - 709. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. W. Clarke, N. Monnier, H. Li, D. Zhou, H. Browne, and D. Klenerman Two-Color Fluorescence Analysis of Individual Virions Determines the Distribution of the Copy Number of Proteins in Herpes Simplex Virus Particles Biophys. J., August 15, 2007; 93(4): 1329 - 1337. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Menotti, A. Cerretani, and G. Campadelli-Fiume A Herpes Simplex Virus Recombinant That Exhibits a Single-Chain Antibody to HER2/neu Enters Cells through the Mammary Tumor Receptor, Independently of the gD Receptors. J. Virol., June 1, 2006; 80(11): 5531 - 5539. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Fusco, C. Forghieri, and G. Campadelli-Fiume The pro-fusion domain of herpes simplex virus glycoprotein D (gD) interacts with the gD N terminus and is displaced by soluble forms of viral receptors PNAS, June 28, 2005; 102(26): 9323 - 9328. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. B. Milne, A. V. Nicola, J. C. Whitbeck, R. J. Eisenberg, and G. H. Cohen Glycoprotein D Receptor-Dependent, Low-pH-Independent Endocytic Entry of Herpes Simplex Virus Type 1 J. Virol., June 1, 2005; 79(11): 6655 - 6663. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Connolly, D. J. Landsburg, A. Carfi, J. C. Whitbeck, Y. Zuo, D. C. Wiley, G. H. Cohen, and R. J. Eisenberg Potential Nectin-1 Binding Site on Herpes Simplex Virus Glycoprotein D J. Virol., January 15, 2005; 79(2): 1282 - 1295. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Zago, C. R. Jogger, and P. G. Spear Use of herpes simplex virus and pseudorabies virus chimeric glycoprotein D molecules to identify regions critical for membrane fusion PNAS, December 14, 2004; 101(50): 17498 - 17503. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Crump, B. Bruun, S. Bell, L. E. Pomeranz, T. Minson, and H. M. Browne Alphaherpesvirus glycoprotein M causes the relocalization of plasma membrane proteins J. Gen. Virol., December 1, 2004; 85(12): 3517 - 3527. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. B. Milne, S. L. Hanna, A. H. Rux, S. H. Willis, G. H. Cohen, and R. J. Eisenberg Function of Herpes Simplex Virus Type 1 gD Mutants with Different Receptor-Binding Affinities in Virus Entry and Fusion J. Virol., August 15, 2003; 77(16): 8962 - 8972. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Connolly, D. J. Landsburg, A. Carfi, D. C. Wiley, G. H. Cohen, and R. J. Eisenberg Structure-Based Mutagenesis of Herpes Simplex Virus Glycoprotein D Defines Three Critical Regions at the gD-HveA/HVEM Binding Interface J. Virol., July 15, 2003; 77(14): 8127 - 8140. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Cairns, R. S. B. Milne, M. Ponce-de-Leon, D. K. Tobin, G. H. Cohen, and R. J. Eisenberg Structure-Function Analysis of Herpes Simplex Virus Type 1 gD and gH-gL: Clues from gDgH Chimeras J. Virol., June 15, 2003; 77(12): 6731 - 6742. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Browne, B. Bruun, A. Whiteley, and T. Minson Analysis of the role of the membrane-spanning and cytoplasmic tail domains of herpes simplex virus type 1 glycoprotein D in membrane fusion J. Gen. Virol., May 1, 2003; 84(5): 1085 - 1089. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. N. Skepper, A. Whiteley, H. Browne, and A. Minson Herpes Simplex Virus Nucleocapsids Mature to Progeny Virions by an Envelopment {right-arrow} Deenvelopment {right-arrow} Reenvelopment Pathway J. Virol., June 15, 2001; 75(12): 5697 - 5702. [Abstract] [Full Text]
|
|
|
|
|
|
H. Bultmann, J. S. Busse, and C. R. Brandt Modified FGF4 Signal Peptide Inhibits Entry of Herpes Simplex Virus Type 1 J. Virol., March 15, 2001; 75(6): 2634 - 2645. [Abstract] [Full Text]
|
|
|
|
|
|
G. Rodger, J. Boname, S. Bell, and T. Minson Assembly and Organization of Glycoproteins B, C, D, and H in Herpes Simplex Virus Type 1 Particles Lacking Individual Glycoproteins: No Evidence for the Formation of a Complex of These Molecules J. Virol., January 15, 2001; 75(2): 710 - 716. [Abstract] [Full Text]
|
|
|
|
 |
|
 J.-A. Liljeqvist, B. Svennerholm, and T. Bergström Conservation of Type-Specific B-Cell Epitopes of Glycoprotein G in Clinical Herpes Simplex Virus Type 2 Isolates J. Clin. Microbiol., December 1, 2000; 38(12): 4517 - 4522. [Abstract] [Full Text]
|
|
|
|
|
|
M. I. Muggeridge Characterization of cell-cell fusion mediated by herpes simplex virus 2 glycoproteins gB, gD, gH and gL in transfected cells J. Gen. Virol., August 1, 2000; 81(8): 2017 - 2027. [Abstract] [Full Text]
|
|
|
|
|
|
M. Lopez, F. Cocchi, L. Menotti, E. Avitabile, P. Dubreuil, and G. Campadelli-Fiume Nectin2alpha (PRR2alpha or HveB) and Nectin2delta Are Low-Efficiency Mediators for Entry of Herpes Simplex Virus Mutants Carrying the Leu25Pro Substitution in Glycoprotein D J. Virol., February 1, 2000; 74(3): 1267 - 1274. [Abstract] [Full Text]
|
|
|
|
|
|
J. C. Whitbeck, M. I. Muggeridge, A. H. Rux, W. Hou, C. Krummenacher, H. Lou, A. van Geelen, R. J. Eisenberg, and G. H. Cohen The Major Neutralizing Antigenic Site on Herpes Simplex Virus Glycoprotein D Overlaps a Receptor-Binding Domain J. Virol., December 1, 1999; 73(12): 9879 - 9890. [Abstract] [Full Text]
|
|
|
|
|
|
A. Whiteley, B. Bruun, T. Minson, and H. Browne Effects of Targeting Herpes Simplex Virus Type 1 gD to the Endoplasmic Reticulum and trans-Golgi Network J. Virol., November 1, 1999; 73(11): 9515 - 9520. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Anderson and U. Gompels N- and C-terminal external domains of human herpesvirus-6 glycoprotein H affect a fusion-associated conformation mediated by glycoprotein L binding the N terminus J. Gen. Virol., June 1, 1999; 80(6): 1485 - 1494. [Abstract]
|
|
|
|
|
|
A. H. Rux, S. H. Willis, A. V. Nicola, W. Hou, C. Peng, H. Lou, G. H. Cohen, and R. J. Eisenberg Functional Region IV of Glycoprotein D from Herpes Simplex Virus Modulates Glycoprotein Binding to the Herpesvirus Entry Mediator J. Virol., September 1, 1998; 72(9): 7091 - 7098. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Terry-Allison, R. I. Montgomery, J. C. Whitbeck, R. Xu, G. H. Cohen, R. J. Eisenberg, and P. G. Spear HveA (Herpesvirus Entry Mediator A), a Coreceptor for Herpes Simplex Virus Entry, also Participates in Virus-Induced Cell Fusion J. Virol., July 1, 1998; 72(7): 5802 - 5810. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. V. Nicola, M. Ponce de Leon, R. Xu, W. Hou, J. C. Whitbeck, C. Krummenacher, R. I. Montgomery, P. G. Spear, R. J. Eisenberg, and G. H. Cohen Monoclonal Antibodies to Distinct Sites on Herpes Simplex Virus (HSV) Glycoprotein D Block HSV Binding to HVEM J. Virol., May 1, 1998; 72(5): 3595 - 3601. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| INT J SYST EVOL MICROBIOL | MICROBIOLOGY | J GEN VIROL |
| J MED MICROBIOL | ALL SGM JOURNALS | |
