Characterization and Establishment of a Novel EBV Strain Simultaneously Associated With Nasopharyngeal Carcinoma and B-Cell Lymphoma.

Fenggang Yu,Nicholas L Syn,Boon Cher Goh,Junyun Lai,Kwok Seng Loh,Yanan Lu,Wei Jian Tan,Lingzhi Wang,Paul A Macary,Qing Yun Chong

doi:10.3389/fonc.2021.626659

Abstract

Epstein-Barr virus (EBV)—the prototypical human tumor virus—is responsible for 1–2% of the global cancer burden, but divergent strains seem to exist in different geographical regions with distinct predilections for causing lymphoid or epithelial malignancies. Here we report the establishment and characterization of Yu103, an Asia Pacific EBV strain with a highly remarkable provenance of being derived from nasopharyngeal carcinoma biopsy but subsequently propagated in human B-lymphoma cells and xenograft models. Unlike previously characterized EBV strains which are either predominantly B-lymphotropic or epitheliotropic, Yu103 evinces an uncanny capacity to infect and transform both B-lymphocytes and nasopharyngeal epithelial cells. Genomic and phylogenetic analyses indicated that Yu103 EBV lies midway along the spectrum of EBV strains known to drive lymphomagenesis or carcinogenesis, and harbors molecular features which likely account for its unusual properties. To our knowledge, Yu103 EBV is currently the only EBV isolate shown to drive human nasopharyngeal carcinoma and B-lymphoma, and should therefore provide a powerful novel platform for research on EBV-driven hematological and epithelial malignancies.

Highlights

Epstein-Barr virus (EBV), the prototypical human tumor virus [1], infects 95% of the human adult population and is etiologically implicated in a spectrum of lymphoid and epithelial malignancies, which exhibit very striking patterns of worldwide distribution
A biopsy was obtained from a 38-year-old Singaporean Chinese male with stage 4 (T3N1M0) nasopharyngeal carcinoma
Development of effective therapies and prophylactic strategies against EBV-driven neoplasia have been severely constrained by our inability to recapitulate the diversity of pathogenic EBV strains in preclinical research, which underscores the importance of expanding our armamentarium of experimental tools

Summary

Introduction

Epstein-Barr virus (EBV), the prototypical human tumor virus [1], infects 95% of the human adult population and is etiologically implicated in a spectrum of lymphoid and epithelial malignancies, which exhibit very striking patterns of worldwide distribution. Hodgkin’s lymphomas feature a much higher prevalence in Europe and North America, Burkitt’s lymphoma is endemic in equatorial Africa, and non-keratinizing nasopharyngeal carcinoma (NPC) in East and Southeast Asia is almost universally associated with EBV infection [2, 3]. The scarcity of in vitro NPC models which stably maintain the viral episome has invariably hampered translational and therapeutic advances, including novel immunotherapies (e.g., adoptive T-cell therapies and therapeutic cancer vaccines directed against EBV epitopes) and prophylactic vaccines whose development are contingent on the ability of preclinical models to recapitulate the repertoire and variation in viral epitopes across different EBV strains [3, 14,15,16]

Methods

Results

Conclusion