ABSTRACT

ANTIGENIC VARIATION OF VARICELLA-ZOSTER VIRUS Fc RECEPTOR gE: LOSS OF A MAJOR B-CELL EPITOPE IN THE ECTODOMAIN

Richard A. Santos, Jorge A. Padilla, Christopher Hatfield and Charles Grose

Varicella zoster virus (VZV) is considered to possess a genetically stable genome; only one serotype is recognized around the world. The 125 kbp genome contains approximately 70 open reading frames. One that has received particular attention is open-reading-frame 68 which codes for glycoprotein gE, the predominant 623-residue viral envelope product which harbors both B-cell and T-cell epitopes. This report describes the initial characterization of a community acquired VZV isolate which was a distinguishable second serotype, i.e., it had lost a major B-cell epitope defined on the gE ectodomain by a murine monoclonal antibody called MAb 3B3. The MAb 3B3 epitope was found not only on the prototype sequenced Dumas strain from Holland and all previously tested North American isolates, but also was present on the varicella vaccine Oka strain originally attenuated in Japan. Sequencing of the mutated gE ectodomain demonstrated that codon 150 exhibited a single base change which led to an amino acid change (aspartic acid to asparagine). Observation of the monolayers infected with the mutant VZV strain also led to the surprising discovery that the topography of egress was altered. Wild type VZV emerges along distinctive viral highways while the mutant strain virions were nearly uniformly distributed over the cell surface in a pattern more closely resembling egress of herpes simplex virus 1. The mutant VZV strain was designated VZV-MSP because it was isolated in the state of Minnesota, U.S.A.

Santos, R., Padilla, J., Hatfield, C. and Grose, C. (1998) Antigenic Variation of Varicella-Zoster Virus Fc Receptor gE: Loss of a Major B-Cell Epitope in the Ectodomain Virology 249, 21-31