Budding of Marburg virus

病毒核衣壳与细胞膜的结合以及随后病毒颗粒从感染细胞中释放（出芽）是一个刚刚开始被理解的过程。直到最近才发现，复杂的细胞出芽机制对于某些病毒如丝状病毒和逆转录病毒的出芽是必需的。丝状病毒出芽的关键参与者是病毒基质蛋白VP40，其一方面协调病毒结构单元（核衣壳和包膜）的组装，另一方面与细胞出芽机制相互作用。VP40篡夺晚期内体隔室的膜（多泡体），用于其自身运输至出芽位点（质膜或多泡体）。此外，VP40将病毒表面蛋白GP和宿主细胞衍生的脂质募集到细胞外周的多泡体，其成为形成病毒包膜的平台。最后，VP40诱导丝状病毒样颗粒的形成，所述丝状病毒样颗粒被释放到培养基中并且非常类似于病毒颗粒。为了更详细地了解马尔堡病毒的出芽过程，我们将解决以下问题：（i）马尔堡病毒VP40如何精确地与细胞出芽机制相互作用？(ii)病毒蛋白NP、VP24和GP如何影响出芽？(iii)病毒包膜的确切脂质组成是什么？其组成是如何调节的？(iv)VP40在空间中是如何组织以诱导丝状形式的VLP和病毒颗粒的？(v)出芽部位是否影响丝状病毒的传染性？

The envelopment of viral nucleocapsids with cellular membranes and the subsequent release of viral particles from the infected cell (budding) is a process that is just at the beginning of being understood. It only recently turned out that a complex cellular budding machinery is necessary for the budding of some viruses e.g. filoviruses and retroviruses. Key player for the budding of filoviruses is the viral matrix protein VP40 that on the one hand orchestrates the assembly of the viral building blocks (nucleocapsid and envelope) and on the other hand interacts with the cellular budding machinery. VP40 usurps membranes of the late endosomal compartment (multivesicular bodies) for its own transport to the sites of budding (plasma membrane or multivesicular bodies). Moreover, VP40 recruits the viral surface protein GP and host cell-derived lipids to multivesicular bodies in the periphery of the cells, which become platforms for the formation of the viral envelope. Finally, VP40 induces the formation of filamentous virus-like particles which are released into the medium and closely resemble viral particles. To understand the budding process of Marburgvirus in more detail we will address following questions: (i) How does Marburgvirus VP40 precisely interact with the cellular budding machinery? (ii) How do the viral proteins NP, VP24, and GP influence budding? (iii) What is the exact lipid composition of the viral envelope and how is its composition regulated? (iv) How is VP40 organized in space to induce the filamentous form of VLPs and viral particles? (v) Does the site of budding influence the infectivity of filoviruses?