Sattler Christine, Steer Beatrix, Adler Heiko
Research Unit Gene Vectors, Helmholtz Zentrum München - German Research Center for Environmental Health (GmbH), Munich, Germany.
PLoS Pathog. 2016 Mar 23;12(3):e1005510. doi: 10.1371/journal.ppat.1005510. eCollection 2016 Mar.
An unresolved question in herpesvirus biology is why some herpesviruses contain more than one lytic origin of replication (oriLyt). Using murine gammaherpesvirus 68 (MHV-68) as model virus containing two oriLyts, we demonstrate that loss of either of the two oriLyts was well tolerated in some situations but not in others both in vitro and in vivo. This was related to the cell type, the organ or the route of inoculation. Depending on the cell type, different cellular proteins, for example Hexim1 and Rbbp4, were found to be associated with oriLyt DNA. Overexpression or downregulation of these proteins differentially affected the growth of mutants lacking either the left or the right oriLyt. Thus, multiple oriLyts are required to ensure optimal fitness in different cell types and tissues.
疱疹病毒生物学中一个尚未解决的问题是,为何有些疱疹病毒含有不止一个裂解性复制起点(oriLyt)。我们以含有两个oriLyt的鼠γ疱疹病毒68(MHV-68)作为模型病毒,证明在某些情况下,两个oriLyt中的任何一个缺失在体外和体内都能被很好地耐受,但在其他情况下则不然。这与细胞类型、器官或接种途径有关。根据细胞类型的不同,发现不同的细胞蛋白,如Hexim1和Rbbp4,与oriLyt DNA相关联。这些蛋白的过表达或下调对缺失左或右oriLyt的突变体的生长有不同影响。因此,需要多个oriLyt来确保在不同细胞类型和组织中的最佳适应性。