Structural studies of viral replication and invasion

病毒复制和侵袭的结构研究

• 批准号: 10544179
• 负责人: Hideki Aihara
• 金额: $ 61.96万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2026-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10544179
• 关键词: Antibodies; Area; Cells; Chromosomes; Complex; Coronavirus; Coronavirus spike protein; Development; Exoribonucleases; Gene Delivery; Genome; Goals; Health; Human; Human T-Cell Leukemia Viruses; Integration Host Factors; Invaded; Laboratories; Life Cycle Stages; Malignant Neoplasms; Molecular; RNA; Receptor Inhibition; Research; Retroviridae; Role; Rous sarcoma virus; Techniques; Viral; Viral Genome; Viral Reverse Transcription; Virus; Virus Replication; antiviral drug development; gene therapy; human pathogen; interest; novel; receptor binding; small molecule; structural biology; tool

Abstract Viruses are a major threat to human health. Our laboratory uses various structural biology techniques to dissect molecular mechanisms of how viruses replicate and invade the host cell or its genome. One area of our major interest is retroviral integration, a critical step in the lifecycle of retroviruses that achieves permanent insertion of the reverse-transcribed viral genome into a host chromosome. We will build on our recent structural studies of the Human T-cell Leukemia virus and Rous sarcoma virus intasomes and further investigate the roles of host factors during integration of these retroviruses. Another area that we are pursuing is the replication of coronavirus RNA genomes and host cell invasion. In particular, we are interested in how a virally encoded exoribonuclease complex facilitates faithful replication of the large RNA genomes of coronaviruses, and how this unique proofreading activity could be modulated by small molecules. We are also investigating inhibition of the receptor binding of the coronavirus spike protein by novel antibodies and antibody-mimics. Overall, the studies proposed in this application will help better understand important RNA-based human pathogens and could aid in the development of antiviral strategies, or alternatively, gene delivery tools useful in research or gene therapy applications.

摘要