Neutralization epitope of varicella zoster virus on native viral glycoprotein gp118 (VZV glycoprotein gpIII)

Abstract

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.