The significance of the individual Meq-clustered miRNAs of Marek's disease virus in oncogenesis
The significance of the individual Meq-clustered miRNAs of Marek's disease virus in oncogenesis
复制标题
马立克氏病病毒个体 Meq 簇 miRNA 在肿瘤发生中的意义
DOI：
10.1099/jgv.0.000013
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发表时间：
2015-03-01
影响因子：
3.8
通讯作者：
Luo, Jun
中科院分区：
文献类型：
--
作者：
Teng, Man;Yu, Zu-Hua;Luo, Jun
马立克氏病病毒（Marek’s disease virus， MDV）是一种重要的致癌α疱疹病毒，可在其天然宿主体内诱导快速发作的t细胞淋巴瘤。由MDV编码的meq簇mirna已被认为在诱导淋巴瘤中发挥潜在的关键作用。利用细菌人工染色体诱变技术，我们目前已经构建了一系列特异性的mirna缺失突变体，并证明这些mirna对MDV的复制不是必需的，并且对发展中的疾病的早期细胞溶解或潜伏阶段没有影响。然而，与亲本GX0101相比，感染突变体GX Delta miR-M2、GX Delta miR-M3、GX Delta miR-M5、GX Delta miR-M9和GX Delta miR-M12的鸟类死亡率从100%降至18%、30%、48%、24%和14%，总肿瘤发病率分别从28%降至8%、4%、120%、8%和0%。我们的数据证实，除了mdv1-miR-M4外，其他meq聚集的mirna也在MDV肿瘤发生中发挥关键作用。需要进一步的工作来阐明触发MD淋巴瘤发展的mirna介导的调控机制。
Marek's disease virus (MDV) is an important oncogenic alphaherpesvirus that induces rapid-onset T-cell lymphomas in its natural hosts. The Meq-clustered miRNAs encoded by MDV have been suggested to play potentially critical roles in the induction of lymphomas. Using the technique of bacterial artificial chromosome mutagenesis, we have presently constructed a series of specific miRNA-deleted mutants and demonstrate that these miRNAs are not essential for replication of MDV and have no effects on the early cytolytic or latent phases of the developing disease. However, compared to the parental GX0101, mortality of birds infected with the mutants GX Delta miR-M2, GX Delta miR-M3, GX Delta miR-M5, GX Delta miR-M9 and GX Delta miR-M12 was reduced from 100% to 18%, 30%, 48%, 24% and 14%, coupled with gross tumour incidence reduction from 28% to 8%, 4%, 120%, 8% and 0%, respectively. Our data confirm that except for mdv1-miR-M4, the other Meq-clustered miRNAs also play critical roles in MDV oncogenesis. Further work will be needed to elucidate the miRNA-mediated regulatory mechanisms that trigger the development of MD lymphomas.