Epstein-Barr virus and human herpesvirus 6 detection in a non-Hodgkin's diffuse large B-cell lymphoma cohort by using RNA sequencing

Abstract

Comprehensive virome analysis of RNA sequence (RNA-seq) data sets from 118 non-Hodgkin's B-cell lymphomas revealed a small subset that is positive for Epstein-Barr virus (EBV) or human herpesvirus 6B (HHV-6B), with one coinfection. EBV transcriptome analysis revealed expression of the latency genes RPMS1, LMP1, and LMP2, with one sample additionally showing a high level of early lytic expression and another sample showing a high level of EBNA2 expression. HHV-6B transcriptome analysis revealed that the majority of genes were transcribed.

Fig 1

EBV and HHV-6B detection in diffuse large B-cell lymphomas. (A) Virus branch of the taxonomy trees for the five virus-positive DLBCL samples. (B) Numbers of viral reads per million human mapped reads. (C) Cluster analysis of EBV transcripts along with a bar graph representing the ratio of EBV lytic-to-latent gene expression for each positive sample.

Fig 2

Viral transcriptome. (A) EBV genome coverage data for EBV-positive DLBCLs. The y axis represents the number of reads at each nucleotide position. The modified EBV Akata genome was split between the BBLF2/3 and the BGLF3.5 lytic genes rather than at the terminal repeats to accommodate coverage of splice junctions for the latency membrane protein LMP2. The scale for sample SRS405439 is set to a maximum read level of 2,000 reads, with scales for the inset displays set to maximum read levels of 100 and 300 reads. The scale for sample SRS405443 is set to a maximum read level of 100 reads. Blue features represent lytic genes, red features represent latent genes, green features represent potential noncoding genes, aquamarine features represent microRNAs, and black features represent nongene features (e.g., repeat regions). (B) HHV-6B genome coverage data for HHV-6B-positive DLBCLs. The scale for sample SRS405408 is set to a maximum read level of 15 reads, while the scale for SRS405443 is set to 50 reads.