Antibody-resistant mutations in cross-reactive and type-specific epitopes of herpes simplex virus 1 glycoprotein B map in separate domains.
To characterize the domains of HSV-1 glycoprotein B (gB), we isolated mutants resistant to monoclonal antibodies with potent neutralizing activity. Partial nucleotide sequencing of the mutations revealed that gB contains two domains comprising discontinuous and continuous amino acids that bind cross-reactive and type-specific neutralizing antibodies. Four mutations in a discontinuous domain, R1435, R233, R1375, and R126, contained substitutions of Tyr278 for His278, His298 for Arg298, Gln274 for Arg274, and Asn273 for Tyr273, respectively. Two mutations in a continuous domain, R1392 and R1397, contained substitutions of Thr32 for Ala32 and Thr47 for Asn47, respectively, and overlapped two other type-specific epitopes. Analysis of the nucleotide sequence of strain KOS showed differences from strain F at four residues proximal to the R1392 mutation and one residue proximal to the R1397 mutation, which explains the failure of HSV-1(F)-specific antibodies to these epitopes to react with KOS. One target site for proteolytic cleavage of gB by cellular enzymes maps at the amino terminus, partially overlapping four HSV-1-specific epitopes.
Kousoulas
K G
KG
Department of Stomatology, School of Dentistry, University of California, San Francisco 94143.
Huo
B
B
Pereira
L
L
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology*; D001483:Base Sequence; D002460:Cell Line; D003429:Cross Reactions; D000939:Epitopes; D008969:Molecular Sequence Data; D009154:Mutation; D009500:Neutralization Tests; D011233:Precipitin Tests; D011499:Protein Processing, Post-Translational; D018139:Simplexvirus / Q000276:immunology*; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000276:immunology
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000939:Epitopes; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus