Genome diversity of Epstein-Barr virus from multiple tumor types and normal infection

Journal of Virology
Anne L PalserPaul Kellam

Abstract

Epstein-Barr virus (EBV) infects most of the world's population and is causally associated with several human cancers, but little is known about how EBV genetic variation might influence infection or EBV-associated disease. There are currently no published wild-type EBV genome sequences from a healthy individual and very few genomes from EBV-associated diseases. We have sequenced 71 geographically distinct EBV strains from cell lines, multiple types of primary tumor, and blood samples and the first EBV genome from the saliva of a healthy carrier. We show that the established genome map of EBV accurately represents all strains sequenced, but novel deletions are present in a few isolates. We have increased the number of type 2 EBV genomes sequenced from one to 12 and establish that the type 1/type 2 classification is a major feature of EBV genome variation, defined almost exclusively by variation of EBNA2 and EBNA3 genes, but geographic variation is also present. Single nucleotide polymorphism (SNP) density varies substantially across all known open reading frames and is highest in latency-associated genes. Some T-cell epitope sequences in EBNA3 genes show extensive variation across strains, and we identify codons under positive ...Continue Reading

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Datasets Mentioned

BETA
ERP001026

Methods Mentioned

BETA
exome sequencing
biopsy
PCR
PCA

Software Mentioned

SBP
Abacas
GARD
Fubar
HyPhy
PhyML
jModelTest
Velvet
VelvetOptimiser
SAMTools

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