Antigenic analysis of a major neutralization site of herpes simplex virus glycoprotein D, using deletion mutants and monoclonal antibody-resistant mutants.
Herpes simplex virus glycoprotein D is a component of the virion envelope and appears to be involved in attachment, penetration, and cell fusion. Monoclonal antibodies against this protein can be arranged in groups on the basis of a number of biological and biochemical properties. Group I antibodies are type common, have high complement-independent neutralization titers, and recognize discontinuous (conformational) epitopes; they are currently being used in several laboratories to study the functions of glycoprotein D. We have used a panel of neutralization-resistant mutants to examine the relationships between these antibodies in detail. We found that they can be divided into two subgroups, Ia and Ib, such that mutations selected with Ia antibodies have little or no effect on binding and neutralization by Ib antibodies and vice versa. In addition, Ia antibodies are able to bind deletion and truncation mutants of glycoprotein D that Ib antibodies do not recognize, suggesting that their epitopes are physically distinct. However, with one exception, Ia and Ib antibodies block each other strongly in binding assays with purified glycoprotein D, whereas antibodies from other groups have no effect. We have therefore defined the sum of the Ia and Ib epitopes as antigenic site 1.
Muggeridge
M I
MI
Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia 19104.
Isola
V J
VJ
Byrn
R A
RA
Tucker
T J
TJ
Minson
A C
AC
Glorioso
J C
JC
Cohen
G H
GH
Eisenberg
R J
RJ
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000956:Antigens, Viral / Q000032:analysis*; D001667:Binding, Competitive; D007118:Immunoassay; D009154:Mutation; D009500:Neutralization Tests; D018139:Simplexvirus / Q000235:genetics / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; D014759:Viral Envelope Proteins; C039447:glycoprotein D, Human herpesvirus 1