Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
Department of Advanced Pharmaceutics, Faculty of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
Viruses. 2022 Feb 14;14(2):382. doi: 10.3390/v14020382.
Marek's disease virus (MDV) causes malignant lymphoma in chickens (Marek's disease, MD). Although MD is currently controlled by vaccination, MDV strains have continuously increased in virulence over the recent decades. Polymorphisms in Meq, an MDV-encoded oncoprotein that serves as a transcription factor, have been associated with the enhanced virulence of the virus. In addition, insertions and deletions in Meq have been observed in MDV strains of higher virulence, but their contribution to said virulence remains elusive. In this study, we investigated the contribution of an insertion (L-Meq) and a deletion in the Meq gene (S-Meq) to its functions and MDV pathogenicity. Reporter assays revealed that both insertion and deletion enhanced the transactivation potential of Meq. Additionally, we generated RB-1B-based recombinant MDVs (rMDVs) encoding each Meq isoform and analyzed their pathogenic potential. rMDV encoding L-Meq indueced the highest mortality and tumor incidence in infected animals, whereas the rMDV encoding S-Meq exhibited the lowest pathogenicity. Thus, insertion enhanced the transactivation activity of Meq and MDV pathogenicity, whereas deletion reduced pathogenicity despite having increased transactivation activity. These data suggest that other functions of Meq affect MDV virulence. These data improve our understanding of the mechanisms underlying the evolution of MDV virulence.
马立克氏病病毒（MDV）可导致鸡的恶性淋巴瘤（马立克氏病，MD）。尽管 MD 目前可通过疫苗接种进行控制，但在过去几十年中，MDV 株的毒力不断增强。Meq 是 MDV 编码的一种致癌蛋白，作为转录因子，其多态性与病毒的增强毒力有关。此外，在毒力较高的 MDV 株中观察到 Meq 基因的插入和缺失，但它们对毒力的贡献仍不清楚。在这项研究中，我们研究了 Meq 基因中的插入（L-Meq）和缺失（S-Meq）对其功能和 MDV 致病性的贡献。报告基因检测显示，插入和缺失均增强了 Meq 的转录激活潜能。此外，我们生成了基于 RB-1B 的编码每种 Meq 同工型的重组 MDV（rMDV），并分析了它们的致病潜力。编码 L-Meq 的 rMDV 诱导感染动物的死亡率和肿瘤发生率最高，而编码 S-Meq 的 rMDV 表现出最低的致病性。因此，插入增强了 Meq 的转录激活活性和 MDV 的致病性，而缺失尽管增加了转录激活活性，但降低了致病性。这些数据表明 Meq 的其他功能影响 MDV 的毒力。这些数据增进了我们对 MDV 毒力进化机制的理解。
