Virus-encoded miR-155 ortholog is an important potential regulator but not essential for the development of lymphomas induced by very virulent Marek's disease virus

Virus-encoded miR-155 ortholog is an important potential regulator but not essential for the development of lymphomas induced by very virulent Marek's disease virus
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病毒编码的 miR-155 直向同源物是一个重要的潜在调节因子,但对于剧毒马立克氏病病毒诱导的淋巴瘤的发展不是必需的

DOI:
10.1016/j.virol.2013.09.017
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发表时间:
2014-01-05
期刊:
影响因子:
3.7
通讯作者:
Luo, Jun
Luo, Jun
中科院分区:
医学3区
文献类型:
--
作者:
Yu, Zu-Hua;Teng, Man;Luo, Jun

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microRNA(miRNA)mdv 1-miR-M4是由致癌的马立克氏病病毒(MDV)编码的功能性miR-155直系同源物,先前已被认为参与MDV的发病机制。利用细菌人工染色体诱变技术,我们目前已经评估了mdv 1-miR-M4在极毒力(vv)MDV毒株GX 0101的肿瘤发生中的潜在作用。出乎意料的是,从病毒基因组中单独缺失Meq簇或mdv 1-miR-M4强烈降低而不是消除其致癌性。与GX 0101相比,突变体GX Delta miR-M4和GX Delta Meq-miR的死亡率分别从100%降低至18%和4%,同时总肿瘤发生率分别从28%降低至22%和8%。我们的数据表明,mdv 1-miR-M4可能是马立克氏病(MD)淋巴瘤的发展中的一个重要的调节器,但不是必要的vvMDV的致癌性。此外,一些其他Meq簇的miRNA也可能在vvMDV诱导淋巴瘤中发挥潜在的关键作用。(C)2013作者爱思唯尔公司出版All rights reserved.
The microRNA (miRNA) mdv1-miR-M4, a functional miR-155 ortholog encoded by oncogenic Marek's disease virus (MDV), has previously been suggested to be involved in MDV pathogenesis. Using the technique of bacterial artificial chromosome mutagenesis, we have presently evaluated the potential role of mdv1-miR-M4 in the oncogenesis of the very virulent (vv) MDV strain GX0101. Unexpectedly, deletions of the Meq-cluster or mdv1-miR-M4 alone from the viral genome strongly decreased rather than abolished its oncogenicity. Compared to GX0101, mortalities of mutants GX Delta miR-M4 and GX Delta Meq-miRs were reduced from 100% to 18% and 4%, coupled with the gross tumor incidence reduction from 28% to 22% and 8%, respectively. Our data suggests that the mdv1-miR-M4 is possibly an important regulator in the development of Marek's disease (MD) lymphomas but is not essential for the oncogenicity of vvMDV. In addition, some of the other Meq-clustered miRNAs may also play potentially critical roles in vvMDV induction of lymphomas. (C) 2013 The Authors. Published by Elsevier Inc. All rights reserved.