Institute of Virology, Freie Universität Berlin, 14163 Berlin, Germany.
Viruses. 2019 Jan 28;11(2):111. doi: 10.3390/v11020111.
Marek's disease virus (MDV) is an oncogenic alphaherpesvirus that infects chickens and integrates its genome into the telomeres of latently infected cells. MDV encodes two proteins, UL12 and UL29 (ICP8), that are conserved among herpesviruses and could facilitate virus integration. The orthologues of UL12 and UL29 in herpes simplex virus 1 (HSV-1) possess exonuclease and single strand DNA-binding activity, respectively, and facilitate DNA recombination; however, the role of both proteins in the MDV lifecycle remains elusive. To determine if UL12 and/or UL29 are involved in virus replication, we abrogated their expression in the very virulent RB-1B strain. Abrogation of either UL12 or UL29 resulted in a severe impairment of virus replication. We also demonstrated that MDV UL12 can aid in single strand annealing DNA repair, using a well-established reporter cell line. Finally, we assessed the role of UL12 and UL29 in MDV integration and maintenance of the latent virus genome. We could demonstrate that knockdown of UL12 and UL29 does not interfere with the establishment or maintenance of latency. Our data therefore shed light on the role of MDV UL12 and UL29 in MDV replication, DNA repair, and maintenance of the latent virus genome.
马立克氏病病毒（MDV）是一种致瘤性的α疱疹病毒，感染鸡并将其基因组整合到潜伏感染细胞的端粒中。MDV 编码两种蛋白，UL12 和 UL29（ICP8），它们在疱疹病毒中保守，可能有助于病毒整合。单纯疱疹病毒 1（HSV-1）中 UL12 和 UL29 的同源物分别具有核酸外切酶和单链 DNA 结合活性，并促进 DNA 重组；然而，这两种蛋白在 MDV 生命周期中的作用仍不清楚。为了确定 UL12 和/或 UL29 是否参与病毒复制，我们在非常强毒力的 RB-1B 株中阻断了它们的表达。阻断 UL12 或 UL29 的表达都会严重损害病毒复制。我们还证明 MDV UL12 可以通过建立的报告细胞系辅助单链退火 DNA 修复。最后，我们评估了 UL12 和 UL29 在 MDV 整合和潜伏病毒基因组维持中的作用。我们可以证明，UL12 和 UL29 的敲低不会干扰潜伏的建立或维持。因此，我们的数据阐明了 MDV UL12 和 UL29 在 MDV 复制、DNA 修复和潜伏病毒基因组维持中的作用。
