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

Research output: Contribution to journalArticlepeer-review

Standard

Genome diversity of Epstein-Barr virus from multiple tumor types and normal infection. / Palser, Anne L; Grayson, Nicholas E; White, Robert E; Corton, Craig; Correia, Samantha; Ba Abdullah, Mohammed M; Watson, Simon J; Cotten, Matthew; Arrand, John R; Murray, Paul G; Allday, Martin J; Rickinson, Alan B; Young, Lawrence S; Farrell, Paul J; Kellam, Paul.

In: Journal of virology, Vol. 89, No. 10, 05.2015, p. 5222-37.

Research output: Contribution to journalArticlepeer-review

Harvard

Palser, AL, Grayson, NE, White, RE, Corton, C, Correia, S, Ba Abdullah, MM, Watson, SJ, Cotten, M, Arrand, JR, Murray, PG, Allday, MJ, Rickinson, AB, Young, LS, Farrell, PJ & Kellam, P 2015, 'Genome diversity of Epstein-Barr virus from multiple tumor types and normal infection', Journal of virology, vol. 89, no. 10, pp. 5222-37. https://doi.org/10.1128/JVI.03614-14

APA

Palser, A. L., Grayson, N. E., White, R. E., Corton, C., Correia, S., Ba Abdullah, M. M., Watson, S. J., Cotten, M., Arrand, J. R., Murray, P. G., Allday, M. J., Rickinson, A. B., Young, L. S., Farrell, P. J., & Kellam, P. (2015). Genome diversity of Epstein-Barr virus from multiple tumor types and normal infection. Journal of virology, 89(10), 5222-37. https://doi.org/10.1128/JVI.03614-14

Vancouver

Palser AL, Grayson NE, White RE, Corton C, Correia S, Ba Abdullah MM et al. Genome diversity of Epstein-Barr virus from multiple tumor types and normal infection. Journal of virology. 2015 May;89(10):5222-37. https://doi.org/10.1128/JVI.03614-14

Author

Palser, Anne L ; Grayson, Nicholas E ; White, Robert E ; Corton, Craig ; Correia, Samantha ; Ba Abdullah, Mohammed M ; Watson, Simon J ; Cotten, Matthew ; Arrand, John R ; Murray, Paul G ; Allday, Martin J ; Rickinson, Alan B ; Young, Lawrence S ; Farrell, Paul J ; Kellam, Paul. / Genome diversity of Epstein-Barr virus from multiple tumor types and normal infection. In: Journal of virology. 2015 ; Vol. 89, No. 10. pp. 5222-37.

Bibtex

@article{ea8551a292804d93b81669f75840d7a0,
title = "Genome diversity of Epstein-Barr virus from multiple tumor types and normal infection",
abstract = "UNLABELLED: 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.IMPORTANCE: Most people in the world are infected by Epstein-Barr virus (EBV), and it causes several human diseases, which occur at very different rates in different parts of the world and are linked to host immune system variation. Natural variation in EBV DNA sequence may be important for normal infection and for causing disease. Here we used rapid, cost-effective sequencing to determine 71 new EBV sequences from different sample types and locations worldwide. We showed geographic variation in EBV genomes and identified the most variable parts of the genome. We identified protein sequences that seem to have been selected by the host immune system and detected variability in known immune epitopes. This gives the first overview of EBV genome variation, important for designing vaccines and immune therapy for EBV, and provides techniques to investigate relationships between viral sequence variation and EBV-associated diseases.",
keywords = "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",
author = "Palser, {Anne L} and Grayson, {Nicholas E} and White, {Robert E} and Craig Corton and Samantha Correia and {Ba Abdullah}, {Mohammed M} and Watson, {Simon J} and Matthew Cotten and Arrand, {John R} and Murray, {Paul G} and Allday, {Martin J} and Rickinson, {Alan B} and Young, {Lawrence S} and Farrell, {Paul J} and Paul Kellam",
note = "Copyright {\textcopyright} 2015, Palser et al.",
year = "2015",
month = may,
doi = "10.1128/JVI.03614-14",
language = "English",
volume = "89",
pages = "5222--37",
journal = "Journal of virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "10",

}

RIS

TY - JOUR

T1 - Genome diversity of Epstein-Barr virus from multiple tumor types and normal infection

AU - Palser, Anne L

AU - Grayson, Nicholas E

AU - White, Robert E

AU - Corton, Craig

AU - Correia, Samantha

AU - Ba Abdullah, Mohammed M

AU - Watson, Simon J

AU - Cotten, Matthew

AU - Arrand, John R

AU - Murray, Paul G

AU - Allday, Martin J

AU - Rickinson, Alan B

AU - Young, Lawrence S

AU - Farrell, Paul J

AU - Kellam, Paul

N1 - Copyright © 2015, Palser et al.

PY - 2015/5

Y1 - 2015/5

N2 - UNLABELLED: 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.IMPORTANCE: Most people in the world are infected by Epstein-Barr virus (EBV), and it causes several human diseases, which occur at very different rates in different parts of the world and are linked to host immune system variation. Natural variation in EBV DNA sequence may be important for normal infection and for causing disease. Here we used rapid, cost-effective sequencing to determine 71 new EBV sequences from different sample types and locations worldwide. We showed geographic variation in EBV genomes and identified the most variable parts of the genome. We identified protein sequences that seem to have been selected by the host immune system and detected variability in known immune epitopes. This gives the first overview of EBV genome variation, important for designing vaccines and immune therapy for EBV, and provides techniques to investigate relationships between viral sequence variation and EBV-associated diseases.

AB - UNLABELLED: 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.IMPORTANCE: Most people in the world are infected by Epstein-Barr virus (EBV), and it causes several human diseases, which occur at very different rates in different parts of the world and are linked to host immune system variation. Natural variation in EBV DNA sequence may be important for normal infection and for causing disease. Here we used rapid, cost-effective sequencing to determine 71 new EBV sequences from different sample types and locations worldwide. We showed geographic variation in EBV genomes and identified the most variable parts of the genome. We identified protein sequences that seem to have been selected by the host immune system and detected variability in known immune epitopes. This gives the first overview of EBV genome variation, important for designing vaccines and immune therapy for EBV, and provides techniques to investigate relationships between viral sequence variation and EBV-associated diseases.

KW - Amino Acid Sequence

KW - Antigens, Viral

KW - Carrier State

KW - Cell Line, Tumor

KW - DNA, Viral

KW - Epitopes, T-Lymphocyte

KW - Epstein-Barr Virus Infections

KW - Epstein-Barr Virus Nuclear Antigens

KW - Genetic Variation

KW - Genome, Viral

KW - Herpesvirus 4, Human

KW - Humans

KW - Phylogeny

KW - Polymorphism, Single Nucleotide

KW - Recombination, Genetic

KW - Viral Matrix Proteins

U2 - 10.1128/JVI.03614-14

DO - 10.1128/JVI.03614-14

M3 - Article

C2 - 25787276

VL - 89

SP - 5222

EP - 5237

JO - Journal of virology

JF - Journal of virology

SN - 0022-538X

IS - 10

ER -