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Viral factors involved in Marek's disease virus (MDV) genome integration

参与马立克氏病病毒（MDV）基因组整合的病毒因子

基本信息

批准号：
208935055
负责人：
Professor Dr. Benedikt Bertold Kaufer, Ph.D.
金额：
--
依托单位：
Institut für Virologie (WE05)
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2011
资助国家：
德国
起止时间：
2010-12-31 至 2015-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/208935055?language=en
关键词：
Viral factors involved Marek disease

项目摘要

Some herpesviruses, including the highly oncogenic Marek’s disease virus (MDV) of chickens, can integrate their genetic material into host telomeres, which ensures viral genome maintenance during latency1, 2. MDV and several other herpesviruses harbor telomeric repeats (TMRs) at either end of their linear genomes3, 4. MDV specifies at both termini a long TMR (mTMR) with variable length and a short TMR (sTMR) with only 6 repeats . We recently demonstrated that the mTMR region is essential for MDV genome integration into host telomeres and that integration is critical for efficient lymphomagenesis and reactivation from latency. However, the role of the sTMR region in MDV replication and integration has remained unclear. MDV also encodes two proteins, pUL12 and ICP8, that may be part of the viral recombination machinery, an interpretation supported by the fact that pUL12 and ICP8 of herpes simplex virus facilitate recombination in vitro. Here, we will test the hypothesis that the sTMR region at the MDV genomic termini and the MDV encoded pUL12 and ICP8 facilitate integration of the virus genome into host telomeres. We will test our hypothesis by two specific aims: 1) To determine the role of the sTMR region in MDV replication, integration, and disease development. 2) To test if the putative MDV pUL12/ICP8 recombinase complex facilitates virus genome integration and if integration requires viral and/or cellular DNA replication.

一些疱疹病毒，包括鸡的高致癌性马立克氏病病毒（MDV），可以将其遗传物质整合到宿主端粒中，这确保了病毒基因组在潜伏期的维持1，2。MDV和其他几种疱疹病毒在其线性基因组的两端都有端粒重复序列（TMR）3，4。MDV在两个末端指定具有可变长度的长TMR（mTMR）和仅具有6个重复的短TMR（sTMR）。我们最近证明了mTMR区域对于MDV基因组整合到宿主端粒中是必不可少的，并且该整合对于有效的淋巴瘤发生和从潜伏期的再激活是至关重要的。然而，sTMR区域在MDV复制和整合中的作用仍不清楚。MDV还编码两种蛋白质，pUL 12和ICP 8，其可能是病毒重组机制的一部分，这一解释得到了单纯疱疹病毒的pUL 12和ICP 8促进体外重组的事实的支持。在这里，我们将测试MDV基因组末端的sTMR区域和MDV编码的pUL 12和ICP 8促进病毒基因组整合到宿主端粒中的假设。我们将通过两个具体目标来检验我们的假设：1）确定sTMR区域在MDV复制、整合和疾病发展中的作用。2)检测推定的MDV pUL 12/ICP 8重组酶复合物是否促进病毒基因组整合，以及整合是否需要病毒和/或细胞DNA复制。