DsRNA Characterization in Monkeypox-infected Cells

猴痘感染细胞中的 DsRNA 表征

• 批准号: 8372121
• 负责人: Bertram L. Jacobs
• 金额: $ 38.3万
• 依托单位: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-24 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8372121
• 关键词: Alleles; Animals; Attenuated; Authorization documentation; Binding; Cell Line; Cells; Centers for Disease Control and Prevention (U.S.); Chromosome Mapping; Complement; Development; Disease; Double-Stranded RNA; E3L gene; E3L protein; Failure; Gel; Genes; Goals; Hela Cells; Homologous Gene; Human; Human Development; Immune; Immune system; Infection; Lead; Length; Maps; Monkeypox; Monkeypox virus; Mus; Mutation; N-terminal; Natural Immunity; Orthopoxvirus; Pancreatic ribonuclease; Pathogenesis; Pharmaceutical Preparations; Phenotype; Poxviridae; Preparation; Production; Protein Binding; Proteins; Public Health; Reagent; Research; Role; Site; Smallpox; Smallpox Viruses; System; Testing; Time; Vaccination; Vaccines; Vaccinia virus; Variant; Viral Proteins; Virulence; Virus; Virus Diseases; Work; base; interest; mouse model; mutant; novel; prevent; programs; research study

DESCRIPTION (provided by applicant): Monkeypox virus and variola virus share about 95% homology, and cause similar diseases in humans. Yet one of the major determinants of orthopoxvirus virulence, the E3L gene, differs significantly between these two closely related viruses. The monkeypox virus homologue of the variola virus (and vaccinia virus) E3L gene, which is an important vaccinia virus innate immune evasion gene, is partially deleted. Since vaccinia virus, when expressing a similarly deleted E3L is attenuated in experimental animals, it is important to understand the role of this variant monkeypox virus innate immune evasion gene in replication and immune evasion of monkeypox virus. The research in this application will characterize the altered genes in monkeypox virus that are compensating for the partial deletion of the monkeypox virus E3L homologue. As such the work described in this application will provide important information on how monkeypox virus causes disease in animals and in humans. Since monkeypox virus is considered to be a re- emerging human public health concern, this research may provide the basis for development of better vaccines for protection against monkeypox virus infection in humans, and for the development of better treatments for people who do become infected with monkeypox virus. PUBLIC HEALTH RELEVANCE: Monkeypox virus has become a re-emerging human public health concern, since the eradication of smallpox led to the decision to halt vaccination that protected humans from monkeypox virus as well as smallpox. The research proposed in this application will investigate how monkeypox virus evades the host immune system, and will likely have direct relevance to decisions on use of anti-poxviral drugs to treat potential human cases of monkeypox.

性状（申请人提供）：猴痘病毒与天花病毒有约95%的同源性，在人类中引起相似的疾病。然而，正痘病毒毒力的主要决定因素之一E3L基因在这两种密切相关的病毒之间存在显著差异。猴痘病毒同源的天花病毒（和牛痘病毒）E3L基因，这是一个重要的牛痘病毒先天免疫逃避基因，被部分删除。由于表达类似缺失的E3L的牛痘病毒在实验动物中是减毒的，因此重要的是理解该变体猴痘病毒先天免疫逃避基因在猴痘病毒复制和免疫逃避中的作用。本申请中的研究将描述猴痘病毒中改变的基因的特征，这些基因补偿猴痘病毒E3L同源物的部分缺失。因此，本申请中描述的工作将提供关于猴痘病毒如何在动物和人类中引起疾病的重要信息。由于猴痘病毒被认为是重新出现的人类公共卫生问题，因此本研究可为开发更好的疫苗以保护人类免受猴痘病毒感染以及为开发更好的治疗方法以治疗感染猴痘病毒的人提供基础。 公共卫生相关性：猴痘病毒已经成为重新出现的人类公共卫生问题，因为天花的根除导致决定停止保护人类免受猴痘病毒和天花的疫苗接种。本申请中提出的研究将调查猴痘病毒如何逃避宿主免疫系统，并且可能与使用抗痘病毒药物治疗潜在人类猴痘病例的决定直接相关。