SVs in EBV genomes. (A-C) Representative examples of intragenic deletions. Integrative genomics viewer images display intragenic deletions within EBV genomes from 3 CAEBV patients. Histograms depict read coverage, with individual gray lines representing sequence reads. (A) In patient UPN257, a near-complete deletion is observed, with minimal evidence of retained alleles. (B) In patient UPN404, partial retention of reads within the deleted region suggests the presence of undeleted alleles. Mean read coverage within the deletion (150×) amounts to 3.5% of the genome-wide average (4264×). (C) Patient UPN417 exhibits a different pattern, with mean read coverage within the deletion reaching 16.8% of the genomic average. (D) Partial deletions affecting EBNA1. Five partial deletions targeting EBNA1 were identified, each involving at least half of the EBV genome. All deletions retained the essential replication origin, oriP. (E) Schematic of EBNA1 interaction between viral and host genomes. EBNA1 binds to both the oriP region within the viral genome and a specific site in the host genome. This binding is crucial for viral genome stability, ensuring that viral replication occurs alongside host DNA during cell division. Consequently, every EBV genome copy must possess oriP, and at least 1 functional EBNA1 copy per cell is required for viral persistence. (F) Coexistence of complete and partial genomes. In patients UPN920, UPN1213, and eBL-Tumor-0007, ∼50% of the remaining allele fraction suggests a balanced coexistence of complete and partial EBV genomes within each cell. (G) Predominance of partial genomes. In contrast, patients UPN1301 and UPN1306 exhibited a lower remaining allele fraction (∼10%), indicating a predominance of partial genomes over complete ones. (H) Genomic inversions. Horizontal lines represent individual EBV genomes, with arcs indicating inversions. In total, 12 EBV genomes harbored inversions. The locations of the C promoter and EBNA genes are also illustrated. In the top 6 genomes (marked with asterisks), inversions seem to disrupt the connection between the C promoter and the EBNA genes. (I) Integration into the human genome. Four EBV genomes, all derived from Burkitt lymphoma patients, were found integrated into the human genome. The GK_BL29 EBV genome integrated into intron 3 of the ANKMY1 gene, potentially forming a fusion between RPMS1 within the viral genome and ANKMY1 in the host genome. The GK_Farage EBV genome integrated within the immunoglobulin heavy chain (IGH) locus. The Namalwa EBV genome integrated into intron 4 of the PPIEL gene. Instances where repetitive sequences obscured the precise location of the SV are marked with an asterisk. Last, the eBL-Tumor-0031 EBV genome integrated into chromosome 12q21.31, a region devoid of annotated genes within a 100-kb radius. GC, gastric carcinoma.
Figure 4.

SVs in EBV genomes. (A-C) Representative examples of intragenic deletions. Integrative genomics viewer images display intragenic deletions within EBV genomes from 3 CAEBV patients. Histograms depict read coverage, with individual gray lines representing sequence reads. (A) In patient UPN257, a near-complete deletion is observed, with minimal evidence of retained alleles. (B) In patient UPN404, partial retention of reads within the deleted region suggests the presence of undeleted alleles. Mean read coverage within the deletion (150×) amounts to 3.5% of the genome-wide average (4264×). (C) Patient UPN417 exhibits a different pattern, with mean read coverage within the deletion reaching 16.8% of the genomic average. (D) Partial deletions affecting EBNA1. Five partial deletions targeting EBNA1 were identified, each involving at least half of the EBV genome. All deletions retained the essential replication origin, oriP. (E) Schematic of EBNA1 interaction between viral and host genomes. EBNA1 binds to both the oriP region within the viral genome and a specific site in the host genome. This binding is crucial for viral genome stability, ensuring that viral replication occurs alongside host DNA during cell division. Consequently, every EBV genome copy must possess oriP, and at least 1 functional EBNA1 copy per cell is required for viral persistence. (F) Coexistence of complete and partial genomes. In patients UPN920, UPN1213, and eBL-Tumor-0007, ∼50% of the remaining allele fraction suggests a balanced coexistence of complete and partial EBV genomes within each cell. (G) Predominance of partial genomes. In contrast, patients UPN1301 and UPN1306 exhibited a lower remaining allele fraction (∼10%), indicating a predominance of partial genomes over complete ones. (H) Genomic inversions. Horizontal lines represent individual EBV genomes, with arcs indicating inversions. In total, 12 EBV genomes harbored inversions. The locations of the C promoter and EBNA genes are also illustrated. In the top 6 genomes (marked with asterisks), inversions seem to disrupt the connection between the C promoter and the EBNA genes. (I) Integration into the human genome. Four EBV genomes, all derived from Burkitt lymphoma patients, were found integrated into the human genome. The GK_BL29 EBV genome integrated into intron 3 of the ANKMY1 gene, potentially forming a fusion between RPMS1 within the viral genome and ANKMY1 in the host genome. The GK_Farage EBV genome integrated within the immunoglobulin heavy chain (IGH) locus. The Namalwa EBV genome integrated into intron 4 of the PPIEL gene. Instances where repetitive sequences obscured the precise location of the SV are marked with an asterisk. Last, the eBL-Tumor-0031 EBV genome integrated into chromosome 12q21.31, a region devoid of annotated genes within a 100-kb radius. GC, gastric carcinoma.

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