Molecular analysis of the Oka vaccine strain of varicella-zoster virus.

Live attenuated Oka vaccine was subjected to molecular analysis, with the long-term goal of identifying genes in the vaccine strain responsible for its attenuation. Complete genomic sequences for both the Oka parent virus and the Oka vaccine virus were determined and compared. There were differences in only 42 bases between the 2 viruses. More than one-third (15/42) of the nucleotide substitutions in V-Oka were found in open reading frame (ORF) 62. These differences were also observed when sequences of Japanese low-passage clinical isolates of varicella-zoster virus (VZV) were compared with the Oka vaccine strain. The ORF62 gene encodes an immediate early (IE) protein, IE62, that is the major transactivator of VZV and, as such, is critical to initiating the VZV gene expression cascade. Several insertions and deletions were also observed in comparing the 2 sequences, largely in the internal tandem repeat units. Functional differences between the 2 types of Oka virus were also examined. Oka vaccine was found to consist of a mixture of different subpopulations, and the parental Oka virus replicates more efficiently than does the vaccine strain. Development of a bacterial artificial chromosome for VZV expression should lead to the discovery of additional differences in wild and vaccine types and, thus, enhance our understanding of the genetic basis for attenuation of the Oka vaccine strain.