Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Kita-18, Nishi-9, Sapporo 060-0818, Japan.
Infect Genet Evol. 2013 Jun;16:137-43. doi: 10.1016/j.meegid.2012.12.032. Epub 2013 Jan 24.
Serotype 1 strains of Marek's disease virus (MDV-1) cause malignant lymphomas in chickens (Marek's disease; MD). Although MD has been controlled by vaccination, field isolates of MDV-1 have tended to increase in virulence and cause MD even in vaccinated chickens. Meq, a putative MDV-1 oncoprotein, resembles the Jun/Fos family of basic leucine zipper (bZIP) transcription factors and can regulate the expression of viral and cellular genes as a homodimer or as a heterodimer with a variety of bZIP family proteins. Sequencing analysis of some of the viral genes of various MDV-1 strains revealed a distinct diversity of and point mutations in Meq, which may contribute to changes in the transcriptional activities of Meq and, consequently, to increases in MDV-1 oncogenicity. However, few reports have characterized MDV-1 strains isolated in Japan. In this study, we established the amino acid sequences of MDV-1 field isolates from Japan in order to determine whether they display a distinct diversity of and point mutations in Meq. In addition, we analyzed the transactivation activities of the Meq proteins in order to evaluate whether the observed mutations affect their functions. Japanese MDV-1 isolates displayed the distinct mutations in basic region 2 (BR2) and proline-rich repeats (PRRs) of the Meq proteins as well as some unique mutations. Reporter assays revealed that the amino acid substitutions in BR2 and the PRRs affected the Meq transactivation activity. These results suggest that the distinct mutations are also present in the Meq proteins of MDV-1 isolates from Japan and affect their transactivation activities.
血清型 1 型马立克氏病病毒 (MDV-1) 可导致鸡的恶性淋巴瘤(马立克氏病;MD)。尽管 MD 已通过疫苗接种得到控制,但 MDV-1 的田间分离株的毒力趋于增加,并导致即使在接种疫苗的鸡中也会发生 MD。Meq 是 MDV-1 的一种推定的致癌蛋白,类似于 Jun/Fos 家族的碱性亮氨酸拉链 (bZIP) 转录因子,可作为同源二聚体或与多种 bZIP 家族蛋白形成异源二聚体来调节病毒和细胞基因的表达。对各种 MDV-1 株的一些病毒基因进行测序分析发现,Meq 存在明显的多样性和点突变,这可能导致 Meq 的转录活性发生变化,从而导致 MDV-1 的致癌性增加。然而,关于日本分离的 MDV-1 株的报道很少。在这项研究中,我们确定了日本分离的 MDV-1 田间分离株的氨基酸序列,以确定它们是否在 Meq 中显示出明显的多样性和点突变。此外,我们分析了 Meq 蛋白的反式激活活性,以评估观察到的突变是否影响它们的功能。日本 MDV-1 分离株的 Meq 蛋白中的 BR2 和富含脯氨酸重复序列(PRRs)显示出明显的突变以及一些独特的突变。报告基因检测表明,BR2 和 PRRs 中的氨基酸取代会影响 Meq 的反式激活活性。这些结果表明,日本 MDV-1 分离株的 Meq 蛋白中也存在明显的突变,并且影响其反式激活活性。