Patria Joseph N, Jwander Luka, Mbachu Ifeoma, Parcells Levi, Ladman Brian, Trimpert Jakob, Kaufer Benedikt B, Tavlarides-Hontz Phaedra, Parcells Mark S
Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA.
Central Diagnostic Laboratory, National Veterinary Research Institute, Vom 930101, Nigeria.
Viruses. 2024 Dec 31;17(1):56. doi: 10.3390/v17010056.
Marek's disease (MD) is a pathology affecting chickens caused by Marek's disease virus (MDV), an acute transforming alphaherpesvirus of the genus . MD is characterized by paralysis, immune suppression, and the rapid formation of T-cell (primarily CD4+) lymphomas. Over the last 50 years, losses due to MDV infection have been controlled worldwide through vaccination; however, these live-attenuated vaccines are non-sterilizing and potentially contributed to the virulence evolution of MDV field strains. Mutations common to field strains that can overcome vaccine protection were identified in the C-terminal proline-rich repeats of the oncoprotein Meq (Marek's RI-Q-encoded protein). These mutations in have been found to be distinct to their region of origin, with high virulence strains obtained in Europe differing from those having evolved in the US. The present work reports on mutations identified in MDV field strains in Nigeria, arising at farms employing different vaccination practices.
DNA was isolated from FTA cards obtained at 12 farms affected by increased MD in the Plateau State, Nigeria. These sequences included partial whole genomes as well as targeted sequences of the oncogenes from these strains. Several of the genes were cloned for expression and their localization ability to interact with the chicken NF-IL3 protein, a putative Meq dimerization partner, were assessed.
Sequence analysis of the genes from these Nigerian field strains revealed an RB1B-like lineage co-circulating with a European Polen5-like lineage, as well as recombinants harboring a combination of these mutations. In a number of these isolates, Meq mutations accumulated in both N-terminal and C-terminal domains.
Our data, suggest a direct effect of the vaccine strategy on the selection of Meq mutations. Moreover, we posit the evolution of the next higher level of virulence MDVs, a very virulent plus plus pathotype (vv++).
马立克氏病（MD）是一种由马立克氏病病毒（MDV）引起的鸡病，MDV是α疱疹病毒属的一种急性转化病毒。MD的特征是麻痹、免疫抑制以及T细胞（主要是CD4 +）淋巴瘤的快速形成。在过去50年中，全球通过疫苗接种控制了MDV感染造成的损失；然而，这些减毒活疫苗并非无菌，并且可能促成了MDV田间毒株的毒力进化。在癌蛋白Meq（马立克氏RI - Q编码蛋白）的C末端富含脯氨酸的重复序列中鉴定出了田间毒株共有的、可克服疫苗保护作用的突变。已发现这些突变在其起源地区有所不同，欧洲获得的高毒力毒株与在美国进化而来的毒株不同。本研究报告了在尼日利亚MDV田间毒株中鉴定出的突变，这些突变出现在采用不同疫苗接种方式的养殖场。
从尼日利亚高原州12个受MD发病率增加影响的养殖场获得的FTA卡中分离DNA。这些序列包括部分全基因组以及这些毒株癌基因的靶向序列。克隆了几个癌基因用于表达，并评估了它们与鸡NF - IL3蛋白（一种假定的Meq二聚化伴侣）相互作用的定位能力。
对这些尼日利亚田间毒株的癌基因进行序列分析发现，一种RB1B样谱系与一种欧洲Polen5样谱系共同传播，以及含有这些突变组合的重组体。在许多这些分离株中，Meq突变在N末端和C末端结构域均有积累。
我们的数据表明疫苗策略对Meq突变的选择有直接影响。此外，我们推测了下一个更高毒力水平的MDV的进化，即一种超强毒++致病型（vv++）。
