Entry of Coronaviruses into Host Cells

冠状病毒进入宿主细胞

• 批准号: 6897155
• 负责人: Gary R Whittaker
• 金额: $ 7.9万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-01 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6897155
• 关键词: Coronaviridae; SARS virus; acidity /alkalinity; chickens; disease /disorder model; endocytosis; fluorescence; host organism interaction; severe acute respiratory syndrome; technology /technique development; tissue /cell culture; virion; virus infection mechanism

DESCRIPTION (provided by applicant): Entry of coronaviruses into host cells is an under-explored area of virology research. In this application, we propose to use infectious bronchitis virus (IBV) of chickens as a model that would be directly applicable to highly pathogenic human coronaviruses, such as SARS-CoV. The major goal of this application is to define basic information regarding the fusion mechanism and route of internalization of IBV. Certain important gaps remain in our understanding of coronavirus entry: specifically 1) the fact that, to date, no virus--cell fusion assays have been employed to study coronavirus entry, and 2) although coronaviruses are generally considered to undergo cell--cell fusion at neutral pH, previous data also suggest a pH-dependent route of entry through endosomes. To address these issues, we have two specific aims: 1 - To develop a virus-cell fusion assay for coronaviruses. Using protocols in our laboratory to study influenza virus--cell fusion, a principal goal is to develop a fluorescence-based virus-cell fusion assay for the coronavirus IBV. 2 - To determine the internalization route of IBV into host cells. We have previously characterized the entry of other viruses using a combination of molecular, pharmacological and morphological approaches. Using similar techniques, a second principal goal is to define the role of endocytosis during IBV entry. Our work is designed not only to elucidate the basic entry mechanism of IBV, but also to serve as a model for coronaviruses in general--especially highly pathogenic human coronaviruses, such as SARS-CoV. IBV would serve as an excellent model system to understand coronavirus entry and fusion, and facilitate the development of future anti-viral drugs.

描述（由申请人提供）：将冠状病毒进入宿主细胞是病毒学研究的一个未探索的领域。在此应用中，我们建议将鸡的传染性支气管炎病毒（IBV）作为一种模型，该模型直接适用于高度致病性的人冠状病毒，例如SARS-COV。该应用程序的主要目的是定义有关IBV融合机制和内在化途径的基本信息。在我们对冠状病毒进入的理解中，某些重要差距仍然存在：特别是1）迄今为止，没有病毒 - 细胞融合测定法研究冠状病毒的进入，而2）尽管通常认为冠状病毒经历细胞 - 细胞 - 细胞 - 在中性pH下的融合，以前的数据还表明了通过内体的进入的pH依赖性途径。为了解决这些问题，我们有两个具体的目的：1-为冠状病毒开发病毒细胞融合测定法。使用实验室中的方案研究流感病毒 - 细胞融合，一个主要目标是为冠状病毒IBV开发基于荧光的病毒细胞融合测定法。 2-确定IBV进入宿主细胞的内在化途径。我们以前曾使用分子，药理和形态学方法的结合来表征其他病毒的进入。使用类似的技术，第二个主要目标是定义IBV进入过程中内吞作用的作用。我们的工作不仅旨在阐明IBV的基本进入机制，还旨在作为冠状病毒的模型，尤其是高度致病的人冠状病毒，例如SARS-COV。 IBV将作为了解冠状病毒进入和融合的出色模型系统，并促进未来的抗病毒药物的发展。

项目成果

Avian infectious bronchitis virus enters cells via the endocytic pathway.

• DOI: 10.1007/978-0-387-33012-9_54
• 发表时间: 2006
• 期刊: Advances in experimental medicine and biology
• 作者: Chu VC;McElroy LJ;Ferguson AD;Bauman BE;Whittaker GR
• 通讯作者: Whittaker GR

Feline aminopeptidase N is not a functional receptor for avian infectious bronchitis virus.

• DOI: 10.1186/1743-422x-4-20
• 发表时间: 2007-02-26
• 期刊: VIROLOGY JOURNAL
• 影响因子: 4.8
• 作者: Chu, Victor C.;McElroy, Lisa J.;Aronson, Jed M.;Oura, Trisha J.;Harbison, Carole E.;Bauman, Beverley E.;Whittaker, Gary R.
• 通讯作者: Whittaker, Gary R.