EBV genome variations enhance clinicopathological features of nasopharyngeal carcinoma in a non-endemic region.
EBV genome variations enhance clinicopathological features of nasopharyngeal carcinoma in a non-endemic region.
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EB病毒基因组变异增强非流行区鼻咽癌的临床病理特征
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鼻咽癌（NPC）是由EB病毒（EBV）感染引起的，在某些地理区域流行。EBV裂解基因BALF 2与病毒再活化密切相关，BALF 2基因变异株H-H-H是我国南方鼻咽癌流行区的致病株。在这里，我们调查这种EBV变异是否也影响日本非流行地区的NPC。对47株日本NPC的EBV分离株进行病毒基因组测序，并与来自日本的其他EBV相关疾病或中国南方的NPC进行比较。日本NPC的EBV基因组与日本其他疾病或地方性NPC的基因组不同;日本NPC不受地方性毒株（BALF 2 H-H-H）的影响，但经常携带2型EBV或地方性NPC中等风险毒株（BALF 2 H-H-L）。7个单核苷酸变异与日本NPC特异性相关，其中6个存在于1型和2型EBV基因组中，表明2型EBV衍生的单倍型的贡献。这一观察结果得到了2型或H-H-L毒株NPC中更高的病毒滴度和更强的病毒再活化的支持。我们的研究结果强调了病毒株和病毒再激活在非地方性NPC发病机制中的重要性。EB病毒（EBV）基因组变异（如BALF 2）与病毒再激活相关，是中国南方等流行地区鼻咽癌（NPC）的危险因素。我们在日本的NPC的EBV分离株中发现了独特的BALF 2基因组变异，这是一个非流行地区，不同于地方性NPC。我们揭示了病毒株及其再活化在非地方性NPC发病机制中的重要性。
Nasopharyngeal carcinoma (NPC) is caused by infection with Epstein–Barr virus (EBV) and endemic in certain geographic regions. EBV lytic gene, BALF2, closely associates with viral reactivation and BALF2 gene variation, the H‐H‐H strain, causes NPC in endemic region, southern China. Here, we investigate whether such EBV variations also affect NPC in a non‐endemic region, Japan. Viral genome sequencing with 47 EBV isolates of Japanese NPC were performed and compared with those of other EBV‐associated diseases from Japan or NPC in Southern China. EBV genomes of Japanese NPC are different from those of other diseases in Japan or endemic NPC; Japanese NPC was not affected by the endemic strain (the BALF2 H‐H‐H) but frequently carried the type 2 EBV or the strain with intermediate risk of endemic NPC (the BALF2 H‐H‐L). Seven single nucleotide variations were specifically associated with Japanese NPC, of which six were present in both type 1 and 2 EBV genomes, suggesting the contribution of the type 2 EBV‐derived haplotype. This observation was supported by a higher viral titer and stronger viral reactivation in NPC with either type 2 or H‐H‐L strains. Our results highlight the importance of viral strains and viral reactivation in the pathogenesis of non‐endemic NPC. Epstein–Barr virus (EBV) genome variation such as BALF2 that is associated with viral reactivation is a risk factor of nasopharyngeal carcinoma (NPC) in endemic regions such as southern China. We found unique BALF2 genome variation in EBV isolates of NPC in Japan, an non‐endemic region, different from endemic NPC. We revealed the importance of viral strains and their reactivation in the pathogenesis of non‐endemic NPC.
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