Elucidation of the Cellular Interactome of Ebola Virus Nucleoprotein and Identification of Therapeutic Targets
Elucidation of the Cellular Interactome of Ebola Virus Nucleoprotein and Identification of Therapeutic Targets
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DOI：
10.1021/acs.jproteome.6b00337
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发表时间：
2016-12-01
影响因子：
4.4
通讯作者：
Hiscox, Julian A.
中科院分区：
文献类型：
--
作者：
Garcia-Dorival, Isabel;Wu, Weining;Hiscox, Julian A.
埃博拉病毒（EBOV）感染导致严重的疾病，在某些情况下致命的出血热。这种感染由7个病毒基因控制，这些基因编码9种病毒蛋白。根据定义，病毒是专性细胞内寄生虫，需要宿主细胞生物学的各个方面来复制其遗传物质，组装新的病毒颗粒，并破坏宿主细胞的抗病毒反应。目前许可的抗病毒药物针对病毒蛋白质以抑制其功能。然而，治疗艾滋病毒和流感病毒的经验表明，耐药病毒很快就会被选中。病毒学中的一个新兴领域是瞬时靶向在病毒生物学中起关键前病毒作用的宿主细胞蛋白，特别是对于急性感染。这具有的优点是，被靶向的蛋白质从病毒的基因组中进化移除。蛋白质组学可以帮助发现生物学，并确定可能被病毒利用以促进感染的细胞蛋白质。这项工作的重点是定义EBOV核蛋白的相互作用组，并确定细胞伴侣，包括HSP 70，与这种蛋白质，以促进稳定性。利用最近Makona分离的基础上的微型基因组复制系统表明，破坏NP的稳定性对病毒RNA的合成产生不利影响。
Ebola virus (EBOV) infection results in severe disease and in some cases lethal hemorrhagic fever. The infection is directed by seven viral genes that encode nine viral proteins. By definition, viruses are obligate intracellular parasites and require aspects of host cell biology in order to replicate their genetic material, assemble new virus particles, and subvert host cell antiviral responses. Currently licensed antivirals are targeted against viral proteins to inhibit their function. However, experience with treating HIV and influenza virus demonstrates that resistant viruses are soon selected. An emerging area in virology is to transiently target host cell proteins that play critical proviral roles in virus biology, especially for acute infections. This has the advantage that the protein being targeted is evolutionary removed from the genome of the virus. Proteomics can aid in discovery biology and identify cellular proteins that may be utilized by the virus to facilitate infection. This work focused on defining the interactome of the EBOV nucleoprotein and identified that cellular chaperones, including HSP70, associate with this protein to promote stability. Utilization of a mini-genome replication system based on a recent Makona isolate demonstrated that disrupting the stability of NP had an adverse effect on viral RNA synthesis.