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Genome Diversity of Epstein-Barr Virus from Multiple Tumor Types and Normal Infection

Title: Genome Diversity of Epstein-Barr Virus from Multiple Tumor Types and Normal Infection
Authors: Palser, AL
Grayson, NE
White, RE
Corton, C
Correia, S
Abdullah, MMB
Watson, SJ
Cotten, M
Arrand, JR
Murray, PG
Allday, MJ
Rickinson, AB
Young, LS
Farrell, PJ
Kellam, P
Item Type: Journal Article
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 selection, both important considerations for the development of vaccines and T-cell therapy. We also provide new evidence for recombination between strains, which provides a further mechanism for the generation of diversity. Our results provide the first global view of EBV sequence variation and demonstrate an effective method for sequencing large numbers of genomes to further understand the genetics of EBV infection.
Issue Date: 1-May-2015
Date of Acceptance: 8-Mar-2015
URI: http://hdl.handle.net/10044/1/26788
DOI: 10.1128/JVI.03614-14
ISSN: 1098-5514
Publisher: American Society for Microbiology
Start Page: 5222
End Page: 5237
Journal / Book Title: Journal of Virology
Volume: 89
Issue: 10
Copyright Statement: © 2015, Palser et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 3.0 Unported license. doi:10.1128/JVI.03614-14
Sponsor/Funder: Imperial College Trust
King Abdulaziz City for Science and Technology (KA
Funder's Grant Number: N/A
N/A
Keywords: Science & Technology
Life Sciences & Biomedicine
Virology
INTERTYPIC RECOMBINANTS
CHINESE POPULATION
AMINO-ACID
SEQUENCE
STRAINS
LYMPHOMAGENESIS
INDIVIDUALS
PHYLOGENIES
ALGORITHMS
SELECTION
Science & Technology
Life Sciences & Biomedicine
Virology
INTERTYPIC RECOMBINANTS
AMINO-ACID
SEQUENCE
LYMPHOMAGENESIS
ALGORITHMS
STRAINS
BIOLOGY
TOOLS
Amino Acid Sequence
Antigens, Viral
Carrier State
Cell Line, Tumor
DNA, Viral
Epitopes, T-Lymphocyte
Epstein-Barr Virus Infections
Epstein-Barr Virus Nuclear Antigens
Genetic Variation
Genome, Viral
Herpesvirus 4, Human
Humans
Phylogeny
Polymorphism, Single Nucleotide
Recombination, Genetic
Viral Matrix Proteins
Cell Line, Tumor
Humans
Herpesvirus 4, Human
Epstein-Barr Virus Infections
Viral Matrix Proteins
DNA, Viral
Epstein-Barr Virus Nuclear Antigens
Antigens, Viral
Epitopes, T-Lymphocyte
Carrier State
Phylogeny
Recombination, Genetic
Amino Acid Sequence
Polymorphism, Single Nucleotide
Genome, Viral
Genetic Variation
Virology
06 Biological Sciences
07 Agricultural and Veterinary Sciences
11 Medical and Health Sciences
Publication Status: Published
Online Publication Date: 2015-04-21
Appears in Collections:Department of Infectious Diseases
Faculty of Medicine