GLOBAL IDENTIFICATION OF CELLULAR INTERACTING PARTNERS FOR ARENAVIRUS Z PROTEIN

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 ARENAV既是研究急性和持续性病毒感染的易处理的实验模型系统，也是临床上重要的人类病原体，引起了人们的极大兴趣。几种阿拉伯病毒，主要是拉萨病毒(LASV)引起人类出血热(HF)疾病，而原型阿拉伯病毒LCMV是研究病毒免疫学和发病机制领域基本概念的极佳工具。此外，有证据表明，LCMV是一种被忽视的具有临床意义的人类病原体。我们的长期目标是对ArenaVirus分子和细胞生物学有一个详细的了解。这些知识将有助于阐明阿拉伯病毒与宿主之间的相互作用和相关疾病，并有助于制定有效的战略来抗击阿拉伯病毒感染，这些病毒感染没有获得许可的疫苗，目前的治疗仅限于使用利巴韦林，因为利巴韦林只有部分有效，而且往往与严重副作用有关。我们已经确定ArenaVirus Z蛋白是病毒出芽的驱动力，并表明LASVZ的出芽活性是由Z上存在真正的晚期(L)结构域PPPY和PTAP介导的。许多被包膜的病毒能够通过其出芽蛋白中存在的L结构域与细胞多泡体相互作用并劫持细胞多泡体机制以逃避细胞。这项建议的重点是确定和功能特征的宿主蛋白，影响Z-介导的萌发。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Arenaviruses merit significant interest both as tractable experimental model systems to study acute and persistent viral infections and as clinically important human pathogens. Several arenaviruses, chiefly Lassa virus (LASV) cause hemorrhagic fever (HF) disease in humans, whereas the prototypic Arenavirus LCMV is a superb workhorse for the investigation of basic concepts in the fields of viral immunology and pathogenesis. In addition, evidence indicates that LCMV is a neglected human pathogen of clinical significance. Our long-term objective is to obtain a detailed understanding of the Arenavirus molecular and cell biology. This knowledge will contribute to the elucidation of Arenavirus-host interactions and associated diseases, and facilitate the development of effective strategies to combat arenaviral infections for which there are not licensed vaccines and current therapy is limited to the use of ribavirin, which is only partially effective and often associated with severe side effects. We have identified the arenavirus Z protein as the driving force of virus budding, and shown that LASV Z budding activity is mediated by the presence of bona fide late (L) domains PPPY and PTAP in Z. Many enveloped viruses are capable, via L domains present in their budding proteins, to interact with and hijack the cellular multivesicular body (MVB) machinery to escape the cell. The focus of this proposal is to identify and functionally characterize host proteins that influence Z-mediated budding.