Institut für Virologie, Freie Universität Berlin, Philippstraße 13, 10115 Berlin, Germany.
Virology. 2013 Mar 15;437(2):110-7. doi: 10.1016/j.virol.2013.01.003. Epub 2013 Feb 9.
Marek's disease virus (MDV) encodes an ubiquitin-specific protease (USP) within its UL36 gene. USP is highly conserved among herpesviruses and was shown to be important for MDV replication and pathogenesis in MDV's natural host, the chicken. To further investigate the role of MDV USP, several recombinant (r) MDVs were generated and their in vitro phenotypes were evaluated using plaque size and growth kinetics assays. We discovered that the N-terminus of pUL36 is essential for MDV replication and could not be complemented by ectopic expression of MDV USP. In addition, we demonstrated that the region located between the conserved glutamine (Q85) and leucine (L106) residues comprising the active site cysteine (C98) is also essential for MDV replication. Based on the analyses of the rMDVs generated here, we concluded that MDV USP likely contributes to the structure and/or stability of pUL36 and affects replication and oncogenesis of MDV beyond its enzymatic activity.
马立克氏病病毒 (MDV) 在其 UL36 基因内编码一个泛素特异性蛋白酶 (USP)。USP 在疱疹病毒中高度保守，并且被证明对 MDV 在 MDV 的天然宿主——鸡中的复制和发病机制很重要。为了进一步研究 MDV USP 的作用，我们生成了几种重组 (r) MDV，并使用蚀斑大小和生长动力学测定评估了它们的体外表型。我们发现 pUL36 的 N 端对于 MDV 复制是必需的，并且不能通过 MDV USP 的异位表达来补充。此外，我们证明了包含活性位点半胱氨酸 (C98) 的保守谷氨酰胺 (Q85) 和亮氨酸 (L106) 残基之间的区域对于 MDV 复制也是必需的。基于对这里生成的 rMDV 的分析，我们得出结论，MDV USP 可能有助于 pUL36 的结构和/或稳定性，并影响 MDV 的复制和致癌作用，超出其酶活性。
