The hepatitis B virus (HBV) is a major cause of hepatocellular carcinoma (HCC), partly driven by viral integration and specific oncogenic HBV variants. However, the biological significance of HBV genomes within lymphoid cells (i.e., peripheral blood mononuclear cells, PBMCs) is unclear. Here, we collected available plasma, PBMC, liver, and tumor from 52 chronic HBV (CHB) carriers: 32 with HCC, 19 without HCC, and one with dendritic cell sarcoma, DCS. Using highly sensitive sequencing techniques, next generation sequencing, and AluPCR, we demonstrate that viral genomes (i.e., HBV DNA, RNA, and cccDNA), oncogenic variants, and HBV-host integration are often found in all sample types collected from 52 patients (including lymphoid cells and a DCS tumor). Viral integration was recurrently identified (n=90 such hits) in genes associated with oncogenic consequences in lymphoid and liver cells. Further, HBV genomes increased in PBMCs derived from 7 additional (treated or untreated) CHB carriers after extracellular mitogen stimulation. Our study shows novel HBV molecular data and replication not only liver, but also within 63.8% of lymphoid cells analyzed (including a representative lymphoid cell malignancy), that was enhanced in ex vivo stimulated PBMC.

乙型肝炎病毒（HBV）是肝细胞癌（HCC）的主要原因，部分由病毒整合和特定的致癌性HBV变异驱动。然而，尚不清楚淋巴样细胞（即外周血单核细胞，PBMC）内HBV基因组的生物学意义。在这里，我们从52种慢性HBV（CHB）携带者中收集了可用的血浆，PBMC，肝脏和肿瘤：32例患有HCC，19例没有HCC，1例患有树突状细胞肉瘤DCS。使用高度灵敏的测序技术，下一代测序和AluPCR，我们证明了从52位患者收集的所有样本类型中经常发现病毒基因组（即HBV DNA，RNA和cccDNA），致癌变体和HBV-宿主整合（包括淋巴样细胞和DCS肿瘤）。在与淋巴样细胞和肝细胞致癌作用相关的基因中，病毒整合被反复鉴定（n = 90）。此外，在细胞外促有丝分裂原刺激后，源自7种其他（治疗或未治疗）CHB载体的PBMC中HBV基因组增加。我们的研究显示，新的HBV分子数据和复制不仅在肝脏，而且在分析的淋巴样细胞（包括代表性淋巴样细胞恶性肿瘤）的63.8％之内，在离体刺激的PBMC。