The Evolutionary and Biological Bases of Host Switching in Viruses

病毒宿主转换的进化和生物学基础

基本信息

批准号：
8496821
负责人：
Colin R. Parrish
金额：
$ 32.57万
依托单位：
CORNELL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-03-01 至 2016-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8496821
关键词：
Address Animal Viruses Animals Area Binding Biological Biological Models Birds Canine Parvovirus Canis familiaris Capsid Capsid Proteins Cells Data Disease Epidemic Equine Influenza Virus Equus caballus Evolution Family Family Felidae Feline panleukopenia virus Felis catus Foxes Future Genes Genetic Grant Hemagglutinin Human Infection Influenza A virus Integration Host Factors Mediating Modeling Morbidity - disease rate Mutagenesis Mutation Nature Neuraminidase Parvovirus Pathway interactions Pattern Prevention Probability Process Raccoons Race Receptor Cell Recording of previous events Research Resistance Role Sampling Shapes Sialic Acids Testing Tissues Trachea Transferrin Receptor Tropism United States Variant Viral Viral Genes Viral Hemagglutinins Virus Virus Diseases Virus Receptors Work arm base comparative deep sequencing fitness infectious disease evolution influenzavirus mammalian genome mortality mutant pandemic disease pathogen prevent programs public health relevance receptor research study sialic acid receptor tissue culture transmission process viral RNA virus host interaction

项目摘要

DESCRIPTION (provided by applicant): Emerging viruses are a pressing biomedical problem, with the potential to cause significant morbidity and mortality. We aim to reveal the evolutionary processes that allow viruses to jump to, and become established in, new host species. We will continue and extend our work on two well characterized animal viruses that have successfully jumped species barriers to dogs in the recent past and which represent powerful and experimentally tractable models for human emerging viruses; the emergence of canine parvovirus (CPV) from feline panleukopenia virus (FPV), and the cross-species transfer of H3N8 equine influenza A virus (EIV) to dogs that resulted in the emergence of a canine influenza virus (CIV) that has been circulating in a limited fashion in the United States for the past 10 years. We will perform detailed studies to determine the evolutionary interactions between these viruses and the different host species and cell receptors they utilize, and which mediates viral emergence. We will investigate three overlapping areas using a synthesis of comparative and experimental approaches: 1. To define the role of intermediate and parallel hosts in cross-species virus transmission and adaptation. We will examine how the transfer of parvoviruses among multiple carnivore hosts influences their emergence, through the creation of evolutionary 'intermediates' that contain combinations of key host specific mutations, or by generating a wider spectrum of variants with the potential to infect previously resistant hosts. 2. To examine the short-term and long-term evolutionary interplay between viral capsids and the cell receptors of susceptible and resistant hosts. We will study variants of the host transferrin receptor type-1 (TfR) genes in a range of carnivore species that are susceptible to different parvoviruses, and examine the long-term evolutionary arms race between host receptor and viral capsid, including the evolutionary footprints present in endogenous parvoviruses. We will experimentally connect the variation of the TfR with that observed in the viral capsid protein. 3. To determine how the evolutionary trajectory of a virus shapes patterns of cross-species transmission and adaptation. Although H3N8 EIV first emerged in horses from birds in 1963, only in the last ~10 years has it jumped to dogs, and on multiple occasions. We will determine whether the extended passage of EIV in horses altered the likelihood of successful cross-species transmission to dogs, and define the viral genes that influence host tropism for dogs, particularly the evolutionary connections between the host sialic acid receptors and the viral hemagglutinin and neuraminidase genes.

描述（由申请人提供）：新兴病毒是一个紧迫的生物医学问题，有可能引起明显的发病率和死亡率。我们旨在揭示允许病毒跳入新宿主物种并建立的进化过程。我们将继续进行并扩展我们的工作，并在最近的两个有特征性的动物病毒上，这些病毒成功地跳到了最近的狗的物种障碍，它们代表了人类新兴病毒的强大且具有实验性的模型。犬类细小病毒（CPV）的出现，从猫池植物病毒（FPV）以及H3N8马流感流感病毒（EIV）的跨物种转移到狗到犬的出现，导致犬类流感病毒（CIV）在过去的10年中一直在有限的时尚中流动。我们将进行详细的研究，以确定这些病毒与它们使用的不同宿主物种和细胞受体之间的进化相互作用，并介导病毒出现。我们将使用比较和实验方法的综合研究三个重叠区域：1。定义中间体和平行宿主在跨物种病毒传播和适应中的作用。我们将通过创建包含关键宿主特异性突变的组合的进化“中间体”，或通过产生更广泛的变体具有感染先前抵抗的宿主的潜力，从而研究多个食肉动物宿主之间细节病毒的转移如何影响其出现。 2。检查病毒包包与易感和抗性宿主的细胞受体之间的短期和长期进化相互作用。我们将研究一系列易受不同细胞视网病毒敏感的食肉动物物种中宿主转铁蛋白受体类型1（TFR）基因的变体，并检查宿主受体和病毒capsid之间的长期进化武器种族，包括内源性parvoviruess中存在的进化足迹。我们将通过实验性地将TFR的变异与在病毒衣壳蛋白中观察到的变化联系起来。 3。确定病毒的进化轨迹如何塑造跨物种传播和适应的模式。尽管H3N8 EIV于1963年首次出现在鸟类的马中，但仅在过去的大约10年中，它才跳到狗身上，并多次跳到狗身上。我们将确定马中EIV的扩展通过是否改变了成功跨物种传播的可能性，并定义了影响狗宿主的托管基因的病毒基因，尤其是宿主唾液酸受体与病毒性血凝集蛋白和神经氨基酶基因之间的进化连接。