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

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 - J. Virol. (2015)

Bottom Line: 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.Here we used rapid, cost-effective sequencing to determine 71 new EBV sequences from different sample types and locations worldwide.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.

View Article: PubMed Central - PubMed

Affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.

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SNP variation across all EBV genomes. (A) Single nucleotide polymorphism (SNP) frequency across 83 unique EBV genomes. The line graph is plotted across the genome showing the number of base positions in a sliding 1,000-nt window where at least one EBV sequence has a SNP relative to the consensus sequence. Repeat regions are masked out in gray. (B) Mean number of codon changes (relative to the consensus of 83 EBV sequences) per gene across the genome, presented as codon changes per 1,000 amino acids to normalize for gene length. Synonymous nucleotide changes are indicated by blue bars and nonsynonymous changes by red bars. The repeat regions within BZLF1, BPLF1, BLLF1, and EBNA1, -2, -3B, and -3C have been masked, and data are provided for the nonrepetitive region only. The right scale shows the percentage of EBV genomes with an intact open reading frame for each gene. BWRF1, EBNA-LP, BHLF1, and LF3 were incompletely assembled due to repetitive regions and were not determined. (C) Numbers of codon changes per gene (means ± standard errors of the means, normalized per kilobase), separated into gene type. Latent genes have an increased number of changes compared to early and late lytic genes. Latency-associated genes also have an increased ratio of nonsynonymous to synonymous coding changes compared to lytic genes.
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Figure 2: SNP variation across all EBV genomes. (A) Single nucleotide polymorphism (SNP) frequency across 83 unique EBV genomes. The line graph is plotted across the genome showing the number of base positions in a sliding 1,000-nt window where at least one EBV sequence has a SNP relative to the consensus sequence. Repeat regions are masked out in gray. (B) Mean number of codon changes (relative to the consensus of 83 EBV sequences) per gene across the genome, presented as codon changes per 1,000 amino acids to normalize for gene length. Synonymous nucleotide changes are indicated by blue bars and nonsynonymous changes by red bars. The repeat regions within BZLF1, BPLF1, BLLF1, and EBNA1, -2, -3B, and -3C have been masked, and data are provided for the nonrepetitive region only. The right scale shows the percentage of EBV genomes with an intact open reading frame for each gene. BWRF1, EBNA-LP, BHLF1, and LF3 were incompletely assembled due to repetitive regions and were not determined. (C) Numbers of codon changes per gene (means ± standard errors of the means, normalized per kilobase), separated into gene type. Latent genes have an increased number of changes compared to early and late lytic genes. Latency-associated genes also have an increased ratio of nonsynonymous to synonymous coding changes compared to lytic genes.

Mentions: The multiple-sequence alignment (Fig. 1B) and detailed gene-by-gene analysis of all 83 EBV genomes strongly suggests that the current EBV genome map annotated in NC_007605 is a good representation of the EBV genome. Consistent with this, the open reading frames were shown to be conserved (Fig. 2B). The EBV genome Saliva1 is derived directly from saliva of a healthy carrier and is the first wild-type EBV genome sequenced that was not selected by immortalization of B cells or derived from a cancer cell (Fig. 1B). The close agreement of this sequence to the NC_007605 reference sequence, with no additional insertions or deletions, indicates that the standard EBV genome map is representative of transmissible saliva strains of EBV. The closest EBV strain (based on the fewest SNPs) to the saliva EBV was HKN19, a spontaneous LCL from Hong Kong. Although the identities of the saliva donors tested were anonymous, the panel did include some Asian donors, so it is likely that this is the basis of the similarity.


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

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 - J. Virol. (2015)

SNP variation across all EBV genomes. (A) Single nucleotide polymorphism (SNP) frequency across 83 unique EBV genomes. The line graph is plotted across the genome showing the number of base positions in a sliding 1,000-nt window where at least one EBV sequence has a SNP relative to the consensus sequence. Repeat regions are masked out in gray. (B) Mean number of codon changes (relative to the consensus of 83 EBV sequences) per gene across the genome, presented as codon changes per 1,000 amino acids to normalize for gene length. Synonymous nucleotide changes are indicated by blue bars and nonsynonymous changes by red bars. The repeat regions within BZLF1, BPLF1, BLLF1, and EBNA1, -2, -3B, and -3C have been masked, and data are provided for the nonrepetitive region only. The right scale shows the percentage of EBV genomes with an intact open reading frame for each gene. BWRF1, EBNA-LP, BHLF1, and LF3 were incompletely assembled due to repetitive regions and were not determined. (C) Numbers of codon changes per gene (means ± standard errors of the means, normalized per kilobase), separated into gene type. Latent genes have an increased number of changes compared to early and late lytic genes. Latency-associated genes also have an increased ratio of nonsynonymous to synonymous coding changes compared to lytic genes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4442510&req=5

Figure 2: SNP variation across all EBV genomes. (A) Single nucleotide polymorphism (SNP) frequency across 83 unique EBV genomes. The line graph is plotted across the genome showing the number of base positions in a sliding 1,000-nt window where at least one EBV sequence has a SNP relative to the consensus sequence. Repeat regions are masked out in gray. (B) Mean number of codon changes (relative to the consensus of 83 EBV sequences) per gene across the genome, presented as codon changes per 1,000 amino acids to normalize for gene length. Synonymous nucleotide changes are indicated by blue bars and nonsynonymous changes by red bars. The repeat regions within BZLF1, BPLF1, BLLF1, and EBNA1, -2, -3B, and -3C have been masked, and data are provided for the nonrepetitive region only. The right scale shows the percentage of EBV genomes with an intact open reading frame for each gene. BWRF1, EBNA-LP, BHLF1, and LF3 were incompletely assembled due to repetitive regions and were not determined. (C) Numbers of codon changes per gene (means ± standard errors of the means, normalized per kilobase), separated into gene type. Latent genes have an increased number of changes compared to early and late lytic genes. Latency-associated genes also have an increased ratio of nonsynonymous to synonymous coding changes compared to lytic genes.
Mentions: The multiple-sequence alignment (Fig. 1B) and detailed gene-by-gene analysis of all 83 EBV genomes strongly suggests that the current EBV genome map annotated in NC_007605 is a good representation of the EBV genome. Consistent with this, the open reading frames were shown to be conserved (Fig. 2B). The EBV genome Saliva1 is derived directly from saliva of a healthy carrier and is the first wild-type EBV genome sequenced that was not selected by immortalization of B cells or derived from a cancer cell (Fig. 1B). The close agreement of this sequence to the NC_007605 reference sequence, with no additional insertions or deletions, indicates that the standard EBV genome map is representative of transmissible saliva strains of EBV. The closest EBV strain (based on the fewest SNPs) to the saliva EBV was HKN19, a spontaneous LCL from Hong Kong. Although the identities of the saliva donors tested were anonymous, the panel did include some Asian donors, so it is likely that this is the basis of the similarity.

Bottom Line: 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.Here we used rapid, cost-effective sequencing to determine 71 new EBV sequences from different sample types and locations worldwide.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.

View Article: PubMed Central - PubMed

Affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.

Show MeSH
Related in: MedlinePlus