Everett Roger D, Murray Jill
MRC Virology Unit, Institute of Virology, University of Glasgow, Church St., Glasgow G11 5JR, Scotland, United Kingdom.
J Virol. 2005 Apr;79(8):5078-89. doi: 10.1128/JVI.79.8.5078-5089.2005.
Infections with DNA viruses commonly result in the association of viral genomes and replication compartments with cellular nuclear substructures known as promyelocytic leukemia protein (PML) nuclear bodies or ND10. While there is evidence that viral genomes can associate with preexisting ND10, we demonstrate in this study by live-cell microscopy that structures resembling ND10 form de novo and in association with viral genome complexes during the initial stages of herpes simplex virus type 1 (HSV-1) infection. Consistent with previous studies, we found that the major ND10 proteins PML, Sp100, and hDaxx are exchanged very rapidly between ND10 foci and the surrounding nucleoplasm in live cells. The dynamic nature of the individual protein molecule components of ND10 provides a mechanism by which ND10 proteins can be recruited to novel sites during virus infection. These observations explain why the genomes and replication compartments of DNA viruses that replicate in the cell nucleus are so commonly found in association with ND10. These findings are discussed with reference to the nature, location, and potential number of HSV-1 prereplication compartments and to the dynamic aspects of HSV-1 genomes and viral products during the early stages of lytic infection.
DNA病毒感染通常会导致病毒基因组和复制区室与被称为早幼粒细胞白血病蛋白(PML)核体或ND10的细胞核亚结构相关联。虽然有证据表明病毒基因组可以与预先存在的ND10相关联,但我们在本研究中通过活细胞显微镜观察证明,在单纯疱疹病毒1型(HSV-1)感染的初始阶段,类似于ND10的结构会从头形成并与病毒基因组复合体相关联。与先前的研究一致,我们发现主要的ND10蛋白PML、Sp100和hDaxx在活细胞中在ND10病灶和周围核质之间非常快速地交换。ND10单个蛋白质分子成分的动态性质提供了一种机制,通过该机制ND10蛋白可以在病毒感染期间被招募到新的位点。这些观察结果解释了为什么在细胞核中复制的DNA病毒的基因组和复制区室如此常见地与ND10相关联。结合HSV-1复制前区室的性质、位置和潜在数量以及裂解感染早期HSV-1基因组和病毒产物的动态方面对这些发现进行了讨论。