Viral Adaptation to Host Selenium Status

病毒对宿主硒状态的适应

基本信息

批准号：
8243623
负责人：
Melinda A. Beck
金额：
$ 36.63万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-04-01 至 2014-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8243623
关键词：
Address Affect Animal Model Animals Antimicrobial Resistance Antioxidants Area Behavior Belief Biological Models Biology Border Crossings Cell Culture Techniques Cells Collaborations Collection Complex Computational Biology Computer Simulation Coxsackie Viruses Cuba Cultured Cells Data Disease Disease Outbreaks Ebola Hemorrhagic Fever Emerging Communicable Diseases Enterovirus Environment Epidemic Evolution Exhibits Experimental Models Fever Genome Genomics Global Warming Goals Grant HIV Health Health system Heart Human Human poliovirus Immune response Immune system In Vitro Infection Infectious Agent Interdisciplinary Study Iron Overload Knockout Mice Laboratories Malaria Malnutrition Medicine Methods Modeling Molecular Molecular Evolution Mus Mutation Myocarditis Nature Nucleotides Nutritional Nutritional status Nutritionist Paralysed Patients Pattern Peripheral Nervous System Diseases Poliomyelitis Polioviruses Population Population Dynamics Population Genetics Process Property RNA Viruses Reporting Research Research Personnel Selenium Severe Acute Respiratory Syndrome Stress System Testing Theoretical model Time Tissues Transcript Travel Tuberculosis Vaccines Viral Viral Genome Virulence Virulent Virus Virus Diseases Vitamin E Work World Health World Health Organization deprivation design driving force glutathione peroxidase improved mouse model multidisciplinary nutrition optic nerve disorder pandemic influenza pathogen public health relevance selenium deficiency selenoprotein tissue tropism tool virology

项目摘要

DESCRIPTION (provided by applicant): Previous work in our laboratory has demonstrated that a human isolate of coxsackievirus B3 replicating in a selenium deficient animal develops specific viral mutations. These viral mutations result in increased virulence of the virus, allowing a normally avirulent virus to become virulent. These same specific stable mutations repeatedly evolve under conditions of nutritional deficiency. In addition, we have recently demonstrated that a nutritionally-deficient human population infected with coxsackievirus A9 (another human enterovirus) exhibited rapid and significant sequence divergence of this virus. Thus, we demonstrated for the first time that the nutritional status of both animals and humans can profoundly influence the genome of a viral pathogen, leading to a new viral strain. Our discovery that host nutritional status is a driving force for viral mutation/evolution, suggested a new area for research, namely the interaction of host nutrition and viral evolutionary processes. We believe that host nutritional status is an underappreciated factor in viral emergence, and that we possess both the laboratory models and the human isolates to make a substantial contribution to elucidating the behavior of virus populations in hosts with suboptimal nutrition. The ultimate, long-term goal of this research is to identify patterns of change in virus populations, on the molecular level, that will facilitate the ability to recognize and predict the emergence and spread of a new or altered pathogen. We propose that host nutritional status has been widely ignored as a driving force for viral evolution, despite the fact that new viral strains, and old viral strains with newly pathogenic properties, often occur in populations with widespread malnutrition. Thus, our studies provide a unique opportunity to understand the interaction between host nutrition and viral genome evolution. This grant is an interdisciplinary study involving the fields of nutrition, virology, evolutionary biology, and computational biology. Our model system will begin as a cell culture study to develop models of virus evolution which will then be tested by expanding into animal models. Finally, we will test the robustness of our models using viral isolates obtained from a human nutritional stress that resulted in viral mutation. PUBLIC HEALTH RELEVANCE: Emerging infectious diseases are a continuing threat to the world's population. Although many factors contribute to the emergence of new pathogens, including travel, global warming, introduction into new species, etc., nutritional status of the host has not been widely considered. This project is designed to understand how selenium nutritional status can impact changes in viral adaptation. The goal is to develop tools to predict outbreaks of emerging infectious diseases.

描述（由申请人提供）：我们实验室之前的工作已经证明，在缺硒动物中复制的柯萨奇病毒 B3 人类分离株会产生特定的病毒突变。这些病毒突变导致病毒毒力增加，使通常无毒力的病毒变得有毒力。这些相同的特定稳定突变在营养缺乏的条件下反复进化。此外，我们最近还证明，感染柯萨奇病毒 A9（另一种人类肠道病毒）的营养缺乏人群表现出该病毒快速且显着的序列差异。因此，我们首次证明动物和人类的营养状况可以深刻影响病毒病原体的基因组，从而产生新的病毒株。我们发现宿主营养状况是病毒突变/进化的驱动力，这提出了一个新的研究领域，即宿主营养与病毒进化过程的相互作用。我们认为，宿主的营养状况是病毒出现的一个未被充分认识的因素，并且我们拥有实验室模型和人类分离株，可以为阐明营养不良的宿主中病毒种群的行为做出重大贡献。这项研究的最终长期目标是在分子水平上确定病毒种群的变化模式，这将有助于识别和预测新的或改变的病原体的出现和传播的能力。我们认为，尽管新病毒株和具有新致病特性的旧病毒株经常出现在普遍营养不良的人群中，但宿主的营养状况作为病毒进化的驱动力已被广泛忽视。因此，我们的研究提供了一个独特的机会来了解宿主营养与病毒基因组进化之间的相互作用。该资助是一项跨学科研究，涉及营养学、病毒学、进化生物学和计算生物学领域。我们的模型系统将从细胞培养研究开始，以开发病毒进化模型，然后通过扩展到动物模型来进行测试。最后，我们将使用从导致病毒突变的人类营养应激中获得的病毒分离株来测试我们模型的稳健性。公共卫生相关性：新出现的传染病对世界人口构成持续威胁。尽管许多因素导致新病原体的出现，包括旅行、全球变暖、新物种的引入等，但宿主的营养状况尚未得到广泛考虑。该项目旨在了解硒营养状况如何影响病毒适应的变化。目标是开发工具来预测新发传染病的爆发。