Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas 77843, USA.
North Carolina State University, College of Veterinary Medicine, 1060 William Moore Drive, Raleigh, North Carolina 27607, USA.
J Gen Virol. 2021 Feb;102(2). doi: 10.1099/jgv.0.001528.
Marek's disease virus (MDV) is a highly cell-associated oncogenic alphaherpesvirus that causes T cell lymphoma in chickens. MDV-encoded Meq and vIL8 proteins play important roles in transformation and early cytolytic infection, respectively. Previous studies identified a spliced transcript, , formed by alternative splicing of and genes in MDV lymphoblastoid tumour cells. To determine the role of Meq-vIL8 in MDV pathogenesis, we generated a recombinant MDV (MDV-meqΔSD) by mutating the splice donor site in the gene to abrogate the expression of Meq-vIL8. As expected, our results show that MDV-meqΔSD virus grows similarly to the parental and revertant viruses in cell culture, suggesting that Meq-vIL8 is dispensable for MDV growth . We further characterized the pathogenic properties of MDV-meqΔSD virus in chickens. Our results show that lack of Meq-vIL8 did not affect virus replication during the early cytolytic phase, as determined by immunohistochemistry analysis and/or viral genome copy number, but significantly enhanced viral DNA load in the late phase of infection in the spleen and brain of infected chickens. In addition, we observed that abrogation of Meq-vIL8 expression reduced the mean death time and increased the prevalence of persistent neurological disease, common features of highly virulent strains of MDV, in inoculated chickens. In conclusion, our study shows that Meq-vIL8 is an important virulence factor of MDV.
马立克氏病病毒（MDV）是一种高度细胞相关的致瘤α疱疹病毒，可导致鸡的 T 细胞淋巴瘤。MDV 编码的 Meq 和 vIL8 蛋白分别在转化和早期细胞溶解感染中发挥重要作用。先前的研究鉴定了一个剪接转录本 ，它是由 MDV 淋巴母细胞瘤细胞中 和 基因的选择性剪接形成的。为了确定 Meq-vIL8 在 MDV 发病机制中的作用，我们通过突变 基因中的剪接供体位点产生了一种重组 MDV（MDV-meqΔSD），从而使 Meq-vIL8 的表达失活。正如预期的那样，我们的结果表明，MDV-meqΔSD 病毒在细胞培养中与亲本和回复病毒的生长相似，表明 Meq-vIL8 对于 MDV 的生长不是必需的。我们进一步表征了 MDV-meqΔSD 病毒在鸡中的致病性。我们的结果表明，缺乏 Meq-vIL8 并不影响早期细胞溶解阶段的病毒复制，如免疫组织化学分析和/或病毒基因组拷贝数所示，但显著增加了感染鸡脾脏和脑中感染后期的病毒 DNA 载量。此外，我们观察到，Meq-vIL8 表达的阻断降低了接种鸡的平均死亡时间，并增加了持续性神经疾病的流行，这是 MDV 高毒力株的共同特征。总之，我们的研究表明，Meq-vIL8 是 MDV 的一个重要毒力因子。
