Neutralization epitope of varicella zoster virus on native viral glycoprotein gp118 (VZV glycoprotein gpIII).
Varicella-zoster virus (VZV) specifies the formation of several glycoproteins, including a 118,000-Da mature structural product (gp118). The biologic and biochemical properties of gp118 were studied after production of murine monoclonal antibodies to both a lowpassage laboratory strain (VZV-32) and an attenuated vaccine strain (VZV-Oka). Structural analyses performed with the three glycosidases endo-beta-N-acetylglucosaminidase H (endoglycosidase H), endo-beta-N-acetylglucosaminidase F (endoglycosidase F), and endo-alpha-N-acetylgalactosaminidase demonstrated that gp118 was predominantly an N-linked complex type glycoprotein built upon a polypeptide backbone of approximately 79,000 Da. Sialic acid residues were present on the mature glycoprotein, but these terminal sugars were absent from the partially glycosylated intermediate forms recovered from monensin-treated infected cultures. Unlike another VZV-specified glycoprotein gp98, no new oligosaccharide moieties were observed on gp118 after addition of tunicamycin to VZV-infected cultures. By plaque reduction assays with a panel of monoclonal antibodies, we defined an epitope on this glycoprotein which elicited a complement-independent neutralizing antibody response of high magnitude. The epitope was highly conserved, since it was present on a laboratory VZV strain, wild type isolates, as well as the attenuated vaccine strain (VZV-Oka). Competitive blocking experiments with the same anti-gp118 monoclonal antibodies indicated that four neutralizing antibodies were directed against similar or identical epitopes whereas one nonneutralizing antibody reacted with a different antigenic site. Thus, this study demonstrates the presence of an immunodominant neutralization epitope on native viral glycoprotein gp118. Under a new consensus nomenclature, this glycoprotein will be designated VZV gpIII.
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Montalvo
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C
Grose
D000911:Antibodies, Monoclonal / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology*; D001667:Binding, Competitive; D002460:Cell Line; D000939:Epitopes / Q000276:immunology; D006023:Glycoproteins / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology*; D006026:Glycoside Hydrolases / Q000378:metabolism; D014645:Herpesvirus 3, Human / Q000032:analysis / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007158:Immunologic Techniques; D008970:Molecular Weight; D008985:Monensin / Q000494:pharmacology; D009500:Neutralization Tests; D014415:Tunicamycin / Q000494:pharmacology; D014764:Viral Proteins / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; D000939:Epitopes; D006023:Glycoproteins; D014764:Viral Proteins; D014415:Tunicamycin; D008985:Monensin; D006026:Glycoside Hydrolases