MOLECULAR VARIABILITY AMONG GEOGRAPHICALLY DISTINCT ISOLATES OF VARICELLA-ZOSTER VIRUS.

V.N. Loparev, D. Rollin & D.S. Schmid
National VZV Laboratory, NCID/DVRD/VEHB, Centers for Disease Control and Prevention, Atlanta, GA

To date, the genomic sequence of three VZV strains (Dumas, Oka vaccine, and Oka parental) has been completely determined. These data have revealed the VZV genome to be extraordinarily stable with only around 0.05% sequence variation between any two strains, consisting of scattered individual point mutations. This high degree of conservation complicates the development of a strategy for performing VZV strain surveillance, a capability that will become essential to varicella monitoring efforts in the U.S. as routine vaccination reduces disease incidence to very low levels. To identify potential regions suitable for phylogenetic analysis we compared the sequence of the OKA parental strain genome (Japan) with that of the Dumas strain (Europe). In these two isolates, nucleotide substitutions occur at average rate of 1 mutation per 1000 bp. Nonetheless, eleven potentially valuable regions ranging in size between 500-1500 bp were targeted for PCR amplification and DNA sequencing of low-passage clinical isolates collected in different parts of North America, Europe, Africa, Australia, and Asia. Phylogenetic analysis of designated areas of the VZV genome indicated that the nucleotide and amino acid sequences diverge into at least two major groups. However three targeted regions in ORF22 in particular allowed us to differentiate subgroups circulating in Japan, North and Central Africa, and South America. Application and extension of this approach for VZV strain surveillance will be discussed.

Corresponding Author: V.N. Loparev, Ph.D., Molecular Biology Team Leader, National VZV Laboratory, NCID/DVRD/VEHB, 1600 Clifton Road, MS G-18, Atlanta, GA 30333, USA