Structural studies of Ebola VP35 mediated immune evasion mechanisms

埃博拉VP35介导的免疫逃避机制的结构研究

• 批准号: 8486375
• 负责人: Gaya K. Amarasinghe
• 金额: $ 35.01万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8486375
• 关键词: Antiviral Agents; Attention; Attenuated; Beryllium; Binding; Biochemical; Biological; Bioterrorism; C-terminal; Categories; Cells; Collaborations; Complement; Complex; Coupled; Data; Disease Outbreaks; Double-Stranded RNA; Double-Stranded RNA Binding Domain; Ebola virus; Elements; Genes; Genetic Transcription; Genome; Goals; Growth; Health; Human; Immune; Immune response; Immune system; Immunosuppression; In Vitro; Indium; Infection; Interferon Activation; Interferons; Knowledge; Laboratories; Lead; Length; Mediating; Methods; Modeling; Molecular; Mutation; N-terminal; Natural Immunity; Nature; Pathogenesis; Pathogenicity; Polymerase; Population; Production; Property; Proteins; RNA; RNA Binding; Reagent; Recombinants; Reporting; Research; Resources; Role; Signal Transduction; Staging; Stress; Structure; Surface; Testing; Therapeutic Intervention; Translations; Vaccines; Viral; Viral Hemorrhagic Fevers; Viral Packaging; Viral Pathogenesis; Viral Proteins; Virulence; Virulence Factors; Virus Diseases; Work; base; cofactor; combat; design; eIF-2 Kinase; human IRF3 protein; improved; in vivo; innovation; insight; interferon regulatory factor-3; loss of function; medical schools; multidisciplinary; mutant; novel diagnostics; novel strategies; novel therapeutics; pathogen; programs; research study; response; therapy design; vaccine development; viral RNA

DESCRIPTION (provided by applicant): Ebola virus is a category A priority pathogen and a causative agent of viral hemorrhagic fever. Enhanced pathogenicity displayed by the Ebola virus is achieved through simultaneous inhibition of host immune responses and enhanced production of viral proteins and RNA. However, the exact nature of the interactions between the Ebola virus and host cells that promote viral infection and propagation are poorly understood. Consequently, no vaccines or antiviral agents against Ebola are currently available. These factors combined, underscore the need for detailed structural and functional characterization of the Ebola viral components. Ebola VP35 protein is an important virulence factor required in several viral lifecycle stages, including viral assembly, genome replication, packaging, viral transcription, and antiviral activity toward the host innate immune system. Overall goal of the research program is to explore host-viral interactions that lead to immune evasion. The proposed study, using recombinantly expressed non-infectious VP35 protein, will examine the structure of VP35 and characterize its antiviral activity using biochemical methods. These studies will significantly improve our understanding of how VP35 functions to enhance viral pathogenesis and facilitate the design of novel diagnostic and therapeutic strategies to disrupt critical host-pathogen interactions.

描述(申请人提供)：埃博拉病毒是A类优先病原体，也是病毒性出血热的病原体。埃博拉病毒表现出的增强致病性是通过同时抑制宿主免疫反应和增加病毒蛋白质和RNA的产生来实现的。然而，埃博拉病毒与促进病毒感染和传播的宿主细胞之间相互作用的确切性质尚不清楚。因此，目前还没有针对埃博拉病毒的疫苗或抗病毒药物。这些因素加在一起，突出了对埃博拉病毒组成部分进行详细的结构和功能描述的必要性。埃博拉VP35蛋白是病毒几个生命周期阶段所需的重要毒力因子，包括病毒组装、基因组复制、包装、病毒转录和对宿主先天性免疫系统的抗病毒活性。该研究计划的总体目标是探索导致免疫逃避的宿主与病毒的相互作用。这项拟议的研究将使用重组表达的非感染性VP35蛋白，检测VP35的结构，并使用生化方法表征其抗病毒活性。这些研究将显著提高我们对VP35如何发挥作用以增强病毒致病机制的理解，并有助于设计新的诊断和治疗策略来破坏关键的宿主-病原体相互作用。

项目成果

[Clinico-immunological variants of extremely severe course of hepatitis B].

[极其严重的乙型肝炎病程的临床免疫学变异]。

• 发表时间: 1989
• 期刊: Sovetskaia meditsina
• 作者: Sorinson,SN;Korochkina,OV;Malysheva,EB;Zhaliauskas,AB;Tsybasova,AI
• 通讯作者: Tsybasova,AI