Association of Epstein-Barr virus genomic alterations with human pathologies

作者：Htet Khine, Yoshitaka Sato, Motoharu Hamada, Miki Umeda, A Iizuka, Shika Son, Haruto Arai, Yuki Kojima, Takahiro Watanabe, Azumi Naruse, Kimitoshi Goto, Koichi Ohshima, Yuta Akutsu, Masato Nakaguro, Akira Satou, Hiromi Kataoka, Yoshinori Ito, Akihisa Sawada, Seiichi Kato, Jun‐ichi Kawada, Takayuki Murata, Yusuke Okuno, Hiroshi Kimura · 发表于：Blood · 年份：2025 · DOI：10.1182/blood.2024028055 · 被引用次数：13 · 研究领域：Viral-associated cancers and disorders、Lymphoma Diagnosis and Treatment、Eosinophilic Disorders and Syndromes

ABSTRACT: Epstein-Barr virus (EBV) infects >90% of humans and is associated with both hematological and epithelial malignancies. Here, we analyzed 990 EBV genomes (319 newly sequenced and 671 from public databases) from patients with various diseases to comprehensively characterize genomic variations, including single nucleotide variations (SNVs) and structural variations (SVs). Although most SNVs were a result of conservative evolution and reflected the geographical origins of the viral genomes, we identified several convergent SNV hot spots within the central homology domain of EBNA3B, the transactivation domain of EBNA2, and the second transmembrane domain of LMP1. These convergent SNVs seem to fine-tune viral protein functionality and immunogenicity. SVs, particularly large deletions, were frequently observed in chronic active EBV disease (28%), EBV-positive diffuse large B-cell lymphoma (48%), extranodal natural killer/T-cell lymphoma (41%), and Burkitt lymphoma (25%), but were less common in infectious mononucleosis (11%), posttransplant lymphoproliferative disorder (7%), and epithelial malignancies (5%). In hematological malignancies, deletions often targeted viral microRNA clusters, potentially promoting viral reactivation and lymphomagenesis. Nondeletion SVs, such as inversions, were also prevalent, with several inversions disrupting the C promoter to suppress latent gene expression, thereby maintaining viral dormancy. Furthermore, recurrent EBNA3B deletions suggeste...