A herpesvirus encoded deubiquitinase is a novel neuroinvasive determinant.
A herpesvirus encoded deubiquitinase is a novel neuroinvasive determinant.
复制标题
DOI：
10.1371/journal.ppat.1000387
复制
发表时间：
2009-04
期刊：
影响因子：
6.7
通讯作者：
Smith GA
中科院分区：
文献类型：
--
作者：
Lee JI;Sollars PJ;Baver SB;Pickard GE;Leelawong M;Smith GA
几种α-疱疹病毒的神经侵袭性是一种不常见的感染过程的基础，包括在外周神经系统的感觉神经元中建立终身潜伏感染。神经系统内的复制和传播需要几种疱疹病毒蛋白，这表明利用神经系统作为生产性感染的利基需要一组由病毒编码的专门功能。最初从外周组织进入神经系统是否也需要专门的病毒功能尚不清楚。在这里，我们表明，一个保守的deubiquitinase结构域嵌入在一个伪狂犬病病毒的结构蛋白，pUL 36，是必不可少的初始神经入侵，但随后的哺乳动物神经系统的神经元内和神经元之间的传输。这些发现表明去泛素化酶通过参与以前未被认识到的神经侵袭的初始步骤而促进神经毒力。疱疹病毒的亚类，如单纯疱疹病毒和伪狂犬病病毒，是神经侵入性病原体。感染后，这些病毒有效地靶向周围神经系统组织，并建立终身感染，无法治愈。已知很少有病原体能够熟练地侵入神经系统，并且疱疹病毒实现神经侵入的机制在很大程度上是未知的。在这项研究中，我们证明了病毒蛋白酶起着关键和特定的作用，允许病毒跨越神经系统的阈值，但随后的复制和脑炎在大脑内的传播是不稳定的。
The neuroinvasive property of several alpha-herpesviruses underlies an uncommon infectious process that includes the establishment of life-long latent infections in sensory neurons of the peripheral nervous system. Several herpesvirus proteins are required for replication and dissemination within the nervous system, indicating that exploiting the nervous system as a niche for productive infection requires a specialized set of functions encoded by the virus. Whether initial entry into the nervous system from peripheral tissues also requires specialized viral functions is not known. Here we show that a conserved deubiquitinase domain embedded within a pseudorabies virus structural protein, pUL36, is essential for initial neural invasion, but is subsequently dispensable for transmission within and between neurons of the mammalian nervous system. These findings indicate that the deubiquitinase contributes to neurovirulence by participating in a previously unrecognized initial step in neuroinvasion. Subsets of herpesviruses, such as herpes simplex virus and pseudorabies virus, are neuroinvasive pathogens. Upon infection, these viruses efficiently target peripheral nervous system tissue and establish a life-long infection for which there is no cure. Very few pathogens are known that invade the nervous system proficiently, and the mechanism by which herpesviruses achieve neuroinvasion is largely unknown. In this study, we demonstrate that a viral protease plays a critical and specific role allowing the virus to cross the threshold of the nervous system, but is dispensable for subsequent replication and encephalitic spread within the brain.
登录
查看更多内容
DOI：
10.1073/pnas.0706295104
发表时间：
2007-12-11
影响因子：
11.1
作者：
Jarosinski, Keith;Kattenhorn, Lisa;Osterrieder, Nikolaus
通讯作者：
Osterrieder, Nikolaus
影响因子：
5.4
作者：
Coller, Kelly Elizabeth;Lee, Joy I-Hsuan;Smith, Gregory Allan
通讯作者：
Smith, Gregory Allan
影响因子：
5.4
作者：
Desai, PJ
通讯作者：
Desai, PJ
影响因子：
5.4
作者：
KNIPE, DM;BATTERSON, W;BUCHAN, A
通讯作者：
BUCHAN, A
影响因子：
5.4
作者：
Antinone, Sarah E.;Smith, Gregory A.
通讯作者：
Smith, Gregory A.