Human antibodies to herpes simplex virus type 1 glycoprotein C are neutralizing and target the heparan sulfate-binding domain.
Human antibodies specific for glycoprotein C (gC1) of herpes simplex virus type 1 (HSV-1) neutralized the virus infectivity and efficiently inhibited attachment of HSV-1 to human HaCaT keratinocytes and to murine mutant L cells expressing either heparan sulfate or chondroitin sulfate at the cell surface. Similar activities were observed with anti-gC1 monoclonal antibody B1C1. In addition to HaCaT and L cells, B1C1 antibody neutralized HSV-1 infectivity in simian GMK AH1 cells mildly pre-treated with heparinase III. Human anti-gC1 antibodies efficiently competed with the binding of gC1 to B1C1 antibody whose epitope overlaps a part of the attachment domain of gC1. Human anti-gC1 and B1C1 antibodies extended survival time of mice experimentally infected with HSV-1. We conclude that in HaCaT cells and in cell systems showing restricted expression of glycosaminoglycans, human and some monoclonal anti-gC1 antibodies can target the cell-binding domain of this protein and neutralize viral infectivity.
Adamiak
Beata
B
Department of Clinical Virology, University of Gothenburg, S-413 46 Göteborg, Sweden. beata.adamiak@microbio.gu.se
Trybala
Edward
E
Mardberg
Kristina
K
Johansson
Maria
M
Liljeqvist
Jan-Ake
JA
Olofsson
Sigvard
S
Grabowska
Agnieszka
A
Bienkowska-Szewczyk
Krystyna
K
Szewczyk
Boguslaw
B
Bergstrom
Tomas
T
D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D001665:Binding Sites; D002460:Cell Line; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D000939:Epitopes / Q000276:immunology; D006497:Heparan Sulfate / Q000378:metabolism; D006561:Herpes Simplex / Q000276:immunology; D018259:Herpesvirus 1, Human / Q000276:immunology*; D006801:Humans; D015603:Keratinocytes / Q000821:virology; D051379:Mice; D009500:Neutralization Tests; D016019:Survival Analysis; D014759:Viral Envelope Proteins / Q000276:immunology*; D053585:Virus Attachment
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000939:Epitopes; D006497:Heparan Sulfate; D014759:Viral Envelope Proteins; C038535:glycoprotein gC, herpes simplex virus type 1