ROTAVIRUS AND NORWALK VIRUS

轮状病毒和诺沃克病毒

• 批准号: 8168527
• 负责人: Bidadi Venkataram Prasad
• 金额: $ 2.15万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-15 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168527
• 关键词: Ammonium Chloride; Animals; Antibodies; Antiviral Agents; BCAR3 gene; Biochemical Genetics; Caliber; Caliciviridae; Calicivirus; Capsid; Cells; Child; Collaborations; Complex; Computer Retrieval of Information on Scientific Projects Database; Diarrhea; Epidemic; Exhibits; Funding; Gastroenteritis; Genetic Transcription; Genome; Goals; Grant; Human; Image; In Vitro; Infection; Influenza A Virus, H5N1 Subtype; Institution; Interferon Type I; Kinetics; Life; Medical; Membrane; Morphogenesis; National Center for Research Resources; Nature; Norovirus; Norwalk virus; Orthoreoviruses; PTPN11 gene; Pathogenicity; Penetration; Proteins; Proteolysis; Reoviridae Infections; Reovirus; Research; Research Personnel; Research Project Grants; Resolution; Resources; Rice; Rotavirus; Source; Structural Protein; Structure; Structure-Activity Relationship; System; United States National Institutes of Health; Virulence; Virus; Work; base; epizootic; global health; helicase; image processing; influenza virus INS1 protein; influenzavirus; inhibitor/antagonist; insight; interest; member; mutant; nanometer; nucleoside triphosphatase; particle; pathogen; protein function; receptor; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Major thrust of our research projects is to understand structure-function relationships in medically important viruses such as rotavirus (NIH AI36040), caliciviruses (NIH P01 AI57788-01 in collaboration with Dr. M.K. Estes), orthoreoviruses (NIH RO1 AI32539 in collaboration with Dr. T. Dermody), and influenza viruses (in collaboration with Dr. Andrew Rice, grant submission in progress). We have been using NCRR funded NCMI facility over years, and we will continue to use this excellent facility. The world-class high resolution imaging and image processing facilities are excellently suited for our projects. Rotavirus: Rotavirus is the major cause of severe, life-threatening gastroenteritis in young children and animals. Rotaviruses are large (1000 ¿), complex, icosahedral assemblies. This virus has been the subject of extensive biochemical, genetic and structural studies because of its medical relevance, intriguing structural complexity, and unique strategies of replication and morphogenesis. We will continue further understanding of the structural basis of rotavirus cell entry, endogenous transcription, viroplasm formation, genome replication and packaging at sub-nanometer resolution using the NCMI cryo-EM facility. Our focus will be particularly on human strains. While some of these studies involve rotavirus particles (1000 ¿ diameter), others that are related to viroplasm formation, genome replication/packaging involving rotavirus non-structural proteins such as NSP2, NSP5, VP1, VP2 and NSP6. In infected cells, these proteins work in concert during viroplasm formation, genome replication/encapsidation. To obtain structural insights into how these rotavirus proteins function, high-resolution cryo-EM analysis is perhaps the only option. Caliciviruses: Caliciviruses, grouped into four genera, are important human and veterinary pathogens with a potential for zoonosis2. In these ssRNA viruses, capsid related functions such as assembly, antigenicity, and receptor interactions are encoded in a single protein that forms an icosahedral capsid. We are interested in obtaining structural information about members of the Caliciviridae. We will continue to use NCMI facility to investigate calicivirus-receptor, and calicivirus-antibody interactions. In addition, we plan to use these resources available at NCMI for characterizing norovirus p41 protein that exhibits helicase/NTPase activities. Noroviruses are causative agents of epidemic diarrhea in humans 3. Orthoreoviruses: The goal of the proposed research is to determine mechanisms of non-enveloped virus internalization, disassembly, and membrane penetration using mammalian reovirus as an experimental system. We will continue to use NCMI facilities to further investigate structural basis for reovirus disassembly and membrane penetration by determining structures of sequential reovirus disassembly intermediates, and that of reovirus mutants selected during persistent reovirus infection (PI viruses), which demonstrate enhanced in vitro kinetics of disassembly and grow in the presence of inhibitors of endosomal acidification (ammonium chloride)4 and proteolysis. Influenza virus NS1 protein: Recent emergence of highly pathogenic avian (H5N1) influenza viruses, their epizootic and panzootic nature, and their association with lethal human infections have raised significant global health concerns. Several studies have underscored the importance of non-structural protein NS1 in the increased pathogenicity and virulence of these strains. NS1, is an antagonist of antiviral type-I interferon (IFN) response in the host.

该副本是使用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这是调查员的机构。 我们的研究项目的主要力量是了解医学上重要病毒的结构功能关系，例如轮状病毒（NIH AI36040），Caliciviruess（NIH P01 AI57788-01）与M.K. Estes博士，Orthoreovires，Orthoreoviress，Orthoreovires合作（NIH RO1 AI32539）与Dr. T. D. Dr. t. dr. t. dryfornation（and）（NIH RO1 ARTHOREOVIRES）（NIH RO1 ARTHEROVER）（提交中的提交）。多年来，我们一直在使用NCRR资助的NCMI设施，我们将继续使用这一出色的设施。世界一流的高分辨率成像和图像处理设施非常适合我们的项目。 轮状病毒：轮状病毒是幼儿和动物严重，威胁生命的胃炎的主要原因。轮状病毒大（1000€），复杂的，二十面体组件。该病毒一直是广泛的生化，遗传和结构研究的主题，因为其医学相关性，有趣的结构复杂性以及复制和形态发生的独特策略。我们将继续进一步了解轮状病毒细胞进入，内源性转录，病毒质的形成，基因组复制和包装的结构基础，该结构是使用NCMI Cryo-EM设备在子纳米分辨率下分辨率的。我们的重点将特别放在人类压力上。尽管其中一些研究涉及轮状病毒颗粒（直径为1000€），而其他研究涉及与病毒质形成相关的，基因组复制/包装非结构性蛋白（例如NSP2，NSP5，VP1，VP1，VP2和NSP6）。在受感染的细胞中，这些蛋白质在病毒质形成，基因组复制/封装过程中共同起作用。为了获得有关这些轮状病毒蛋白如何功能的结构见解，高分辨率冷冻EM分析可能是唯一的选择。 蜡膜病毒：将四个属分为四个属的腔室是重要的人类病原体和兽医病原体2。在这些ssRNA病毒中，将相关的相关功能（例如组装，抗原性和受体相互作用）编码在形成冰状体衣壳的单个蛋白质中。我们有兴趣获取有关蓝囊科成员的结构信息。我们将继续使用NCMI设施来研究彩色病毒受体和蜡囊抗体相互作用。此外，我们计划使用NCMI上可用的这些资源来表征表现出热解/NTPase活性的Norovirus P41蛋白。北病毒是人类流行腹泻的灾难性药物3。 矫形病毒：拟议的研究的目的是确定使用哺乳动物依伏修病毒作为实验系统的非发育病毒内在化，拆卸和膜穿透的机制。我们将继续使用NCMI设施来进一步研究葡萄病毒拆卸和膜渗透的结构基础，通过确定顺序的蒸发液的结构拆卸中间体的结构，以及在持久性旋转旋转病毒感染（PI）病毒中选择的孢子病毒突变体的结构，这表现出增强的二酸酸化和生长，以增强型的生长，以实现良好的动力学生长。 （氯化铵）4和蛋白水解。 流感病毒NS1蛋白：高度致病性鸟类（H5N1）的最新出现影响病毒，它们的epizootic和panzootic性质以及它们与致命的人类感染的关联引起了重大的全球健康问题。多项研究削弱了非结构蛋白NS1在这些菌株的致病性和病毒增加中的重要性。 NS1是宿主中抗病毒I型干扰素（IFN）反应的拮抗剂。