VZV Foundation - A Decade Of Leadership In The Fight Against VZV Infections

	Oral Presentation Abstracts: 31 [31] GENOMICS OF VZV-MSP: AN ANALYSIS OF SINGLE NUCLEOTIDE POLYMORPHISMS (SNPs) IN THE VZV GENOME Benjamin Faga, Wendy Maury and *Charles Grose Departments of Microbiology and Pediatrics, University of Iowa, Iowa City, Iowa VZV-MSP is a newly discovered VZV strain that exhibits a distinctive genotype and phenotype. As part of our genetic analysis, >20 kb in the VZV-MSP genome have been sequenced to date and compared with the VZV-Dumas sequence. The VZV-MSP genotype included numerous polymorphisms, including one on the gE ectodomain (D150N) distinguishing VZV-MSP by its loss of a B cell epitope. Recent studies have documented a phenotype specific to VZV-MSP in both infected cells and the SCID-hu model of VZV infection, namely, an accelerated cell-to-cell spread function. In order to understand the significance of the genetic changes in the VZV-MSP genome, we hypothesized that a strategy undertaken by the Human Genome Project could be applied toward the VZV genome, namely SNP analysis. SNPs are the most common genetic change in the human genome; they are sites that contain single base pair variations. At the present time there is an enormous effort to define SNPs in the human genome, because a single SNP in one gene can serve as a genetic marker for a specific disease. Human geneticists have estimated that sequencing the same gene in 8-10 unrelated individuals can uncover most SNPs. To the same end, we sequenced 6 VZV genes from 10 unrelated VZV strains collected from 3 countries, as well as several states within the USA. When compared with the Netherlands Dumas sequence, we discovered a total of 34 SNPs in the 60 VZV genes. Of interest, the viruses clustered on the basis of 85% shared SNPs into four groups. SNPs in the VZV genome correlated with hot spots in the genomes of other herpesviruses, eg, the gH homolog gene in HSV, BHV, PRV and THV. Conversely, the absence of SNPs defined genes and domains within genes required for a conserved function, eg, protein kinases. Finally, as with human populations, VZV SNP analysis demonstrated distinctive SNP profiles related to common ancestry and/or geographic origin; ie, VZV can be distinguished worldwide on the basis of genotype. VZV-MSP represented a contemporary mutation of a Northern European virus. Corresponding Author: Charles Grose, University Hospital/2501JCP, 200 Hawkins Drive, Iowa City, IA 52242, USA

[31]

GENOMICS OF VZV-MSP: AN ANALYSIS OF SINGLE NUCLEOTIDE POLYMORPHISMS (SNPs) IN THE VZV GENOME

Benjamin Faga, Wendy Maury and *Charles Grose
Departments of Microbiology and Pediatrics, University of Iowa, Iowa City, Iowa

VZV-MSP is a newly discovered VZV strain that exhibits a distinctive genotype and phenotype. As part of our genetic analysis, >20 kb in the VZV-MSP genome have been sequenced to date and compared with the VZV-Dumas sequence. The VZV-MSP genotype included numerous polymorphisms, including one on the gE ectodomain (D150N) distinguishing VZV-MSP by its loss of a B cell epitope. Recent studies have documented a phenotype specific to VZV-MSP in both infected cells and the SCID-hu model of VZV infection, namely, an accelerated cell-to-cell spread function.
In order to understand the significance of the genetic changes in the VZV-MSP genome, we hypothesized that a strategy undertaken by the Human Genome Project could be applied toward the VZV genome, namely SNP analysis. SNPs are the most common genetic change in the human genome; they are sites that contain single base pair variations. At the present time there is an enormous effort to define SNPs in the human genome, because a single SNP in one gene can serve as a genetic marker for a specific disease. Human geneticists have estimated that sequencing the same gene in 8-10 unrelated individuals can uncover most SNPs. To the same end, we sequenced 6 VZV genes from 10 unrelated VZV strains collected from 3 countries, as well as several states within the USA. When compared with the Netherlands Dumas sequence, we discovered a total of 34 SNPs in the 60 VZV genes. Of interest, the viruses clustered on the basis of 85% shared SNPs into four groups. SNPs in the VZV genome correlated with hot spots in the genomes of other herpesviruses, eg, the gH homolog gene in HSV, BHV, PRV and THV. Conversely, the absence of SNPs defined genes and domains within genes required for a conserved function, eg, protein kinases. Finally, as with human populations, VZV SNP analysis demonstrated distinctive SNP profiles related to common ancestry and/or geographic origin; ie, VZV can be distinguished worldwide on the basis of genotype. VZV-MSP represented a contemporary mutation of a Northern European virus.

Corresponding Author: Charles Grose, University Hospital/2501JCP, 200 Hawkins Drive, Iowa City, IA 52242, USA