ANTIGENIC VARIATION OF VARICELLA-ZOSTER VIRUS FC RECEPTOR GE - LOSS OF A MAJOR B-CELL EPITOPE IN THE ECTODOMAIN

Varicella tester virus (VZV) is considered to possess a genetically st able genome; only one serotype is recognized around the world. The 125 -kbp genome contains similar to 70 open reading frames. One that has r eceived particular attention is open reading frame 68, which codes for glycoprotein gE, the predominant 623-residue viral envelope product t hat harbors both B and T cell epitopes. This report describes the init ial characterization of a community-acquired VZV isolate that was a di stinguishable second serotype (i.e., it had lost a major B cell epitop e defined on the gE ectodomain by a murine monoclonal antibody called mAb 3B3). The mAb 3B3 epitope was found not only on the prototype sequ enced Dumas strain from Holland and all previously tested North Americ an isolates but also on the varicella vaccine Oka strain originally at tenuated in Japan. Sequencing of the mutated gE ectodomain demonstrate d that codon 150 exhibited a single base change that led to an amino a cid change (aspartic acid to asparagine). Observation of the monolayer s infected with the mutant VN strain also led to the surprising discov ery that the topography of egress was altered. Wild-type VN emerges al ong distinctive viral highways, whereas 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 VN str ain was designated VZV-MSP because it was isolated in Minnesota. (C) 1 998 Academic Press.