Molecular mechanisms of primary and secondary envelopment in herpesvirus morphogenesis

疱疹病毒形态发生中初级和次级包膜的分子机制

• 批准号: 12694498
• 负责人: Professor Dr. Thomas C. Mettenleiter
• 金额: --
• 依托单位: Institut für molekulare Virologie und Zellbiologie (IMVZ)
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2005
• 资助国家: 德国
• 起止时间: 2004-12-31 至 2012-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/12694498?language=en
• 关键词: Molecular; mechanisms; primary; secondary; envelopment

Virion formation and egress of herpesviruses involve two separate budding steps which are differentiated by the subcellular compartments in which they occur and the proteins involved. Primary envelopment of intranuclear genome-containing nucleocapsids at the inner nuclear membrane is followed by fusion of the primary envelope with the outer nuclear membrane resulting in release of nucleocapsids into the cytoplasm. Secondary (and final) envelopment then occurs after addition of the tegument by budding of intracytoplasmic nucleocapsids into vesicles in the trans- Golgi network. Although several of the viral proteins involved have been identified and functionally characterized, the molecular interactions that govern both processes are still largely unclear. We will focus on two areas: (i) identification of virally encoded components of the primary envelope and tegument, and elucidation of interaction between them and intranuclear nucleocapsids, and between viral and cellular nuclear proteins to clarify the molecular basis for primary envelopment; and (ii) interaction between virally encoded components of the secondary envelope and tegument with cytoplasmic nucleocapsids to gain more insight into the basis of secondary envelopment. In addition, the requirements for transport of vesicles containing enveloped virions to the cell surface followed by release of mature herpes virions will be investigated.

疱疹病毒的病毒体形成和排出涉及两个独立的出芽步骤，这两个步骤由它们发生的亚细胞区室和所涉及的蛋白质区分。含有核内基因组的核衣壳在内核膜处的初级包被，随后初级包被与外核膜融合，导致核衣壳释放到细胞质中。在加入被膜后，胞质内的核衣壳出芽形成高尔基体网络中的囊泡，从而发生第二次（也是最后一次）分裂。尽管已经鉴定出了几种相关的病毒蛋白质并进行了功能表征，但控制这两个过程的分子相互作用在很大程度上仍然不清楚。我们将集中在两个方面：（i）鉴定病毒编码的初级包膜和皮层成分，并阐明它们与核内核衣壳之间的相互作用，以及病毒与细胞核蛋白之间的相互作用，以阐明初级包膜的分子基础;以及（ii）次级包膜和皮层的病毒编码组分与细胞质核衣壳之间的相互作用，以更深入地了解二级预防。此外，将研究将含有包膜病毒体的囊泡转运至细胞表面，然后释放成熟疱疹病毒体的要求。