Small viral RNAs as determinants of influenza A virus pathogenesis

小病毒 RNA 作为甲型流感病毒发病机制的决定因素

• 批准号: 10097984
• 负责人: Benjamin R. tenOever
• 金额: $ 42.38万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-04 至 2021-09-06
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10097984
• 关键词: Antiviral Agents; Binding; Binding Sites; Biology; Cell Nucleus; Cells; Code; Complex; Conflict (Psychology); Data; Detection; Development; Ensure; Epidemic; Future; Generations; Genes; Genome; Grant; Immune response; Infection; Influenza A virus; Knowledge; Length; Life Cycle Stages; Mediating; Nature; Nucleotides; Pathogenesis; Phenotype; Play; Polymerase; Population; Positioning Attribute; Process; Production; Proteins; RNA; RNA Interference; RNA-Directed RNA Polymerase; Recombinants; Recording of previous events; Research; Role; Small RNA; Specificity; Structure; System; Technology; Therapeutic; Time; Transcript; Untranslated RNA; Vaccines; Viral; Viral Pathogenesis; Viral Physiology; Virus; Virus Diseases; Virus Replication; combat; cytotoxicity; differential expression; endonuclease; experimental study; improved; next generation sequencing; novel therapeutics; pandemic disease; response; transcriptome sequencing; vaccine development; viral RNA

With just ten major proteins, influenza A virus (IAV) must gain entry to both cell and nucleus, transcribe and replicate its genome, and then perform the inverse of the entry process in order to egress and spread. To achieve this, the virus must introduce new components that change viral biology as the infection progresses. We believe one major component that orchestrates these changes derives from small virus-encoded RNAs (svRNAs) that engage and modulate the viral RNA dependent RNA polymerase (RdRp). This grant focuses on defining how svRNAs change the function of the viral RdRp during the course of infection. The knowledge gained from these studies will significantly contribute to our understanding of IAV biology and may provide an entirely new direction towards the future development of novel therapeutics.

甲型流感病毒（IAV）只有十种主要蛋白质，必须进入细胞和细胞核，转录和复制其基因组，然后执行进入过程的逆过程，以便逸出和传播。为了实现这一目标，病毒必须引入新的成分，随着感染的进展改变病毒生物学。我们相信，协调这些变化的一个主要成分源自小病毒编码的 RNA (svRNA)，它们参与并调节病毒 RNA 依赖性 RNA 聚合酶 (RdRp)。这笔资助的重点是确定 svRNA 在感染过程中如何改变病毒 RdRp 的功能。从这些研究中获得的知识将极大地有助于我们对 IAV 生物学的理解，并可能为新型疗法的未来发展提供全新的方向。