Predicting genetic determinants of Zika virus emergence

预测寨卡病毒出现的遗传决定因素

• 批准号: 9284379
• 负责人: Gregory David Ebel
• 金额: $ 22.79万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-06 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9284379
• 关键词: Aedes; American; Americas; Arboviruses; Asians; Brazil; Chikungunya virus; Clinical; Competence; Complex; Computational Biology; Culex (Genus); Culicidae; Data; Dengue; Dengue Hemorrhagic Fever; Dengue Shock Syndrome; Disease Outbreaks; Eastern Equine Encephalomyelitis; Emerging Communicable Diseases; Environment; Epidemic; Evolution; Experimental Designs; Flavivirus; Foundations; Gabon; Genetic; Genetic Determinism; Genetic Variation; Genome; Geography; Health; Hemolymph; Human; Incidence; Infection; Island; Knowledge; Lead; Literature; Midgut; Mutation; Population; Population Genetics; Process; Publishing; Readiness; Research; Role; Saliva; Salivary Glands; Shapes; South America; Structure; Syndrome; System; Temperature; Time; Tissues; Travel; Uganda; Viral; Viral Genome; Virus; West Nile virus; Work; Zika Virus; base; experience; experimental study; fitness; forest; genetic predictors; grasp; in vivo; transmission process; vector; vector mosquito; vector transmission; virus genetics; virus host interaction

This proposal is for a new R21, Predicting genetic determinants of Zika virus emergence. This project aims to take a proactive approach to assessing how Zika may adapt to American vectors. Ultimately, this research will contribute to an expanding body of data and knowledge in the PI’s lab regarding the impact of specific, ecologically relevant vectors and hosts on arbovirus fitness determinants and population genetics. In particular, in this project we will determine how infection of Ae. aegypti, Ae. albopictus and Cx. quinquefasciatus influence ZIKV genetics. We will also assess the role of ambient temperature in shaping virus populations. Aim 1 focuses on characterizing vector competence of mosquito strains that originate from the Americas for the Asian lineage of ZIKV (i.e. the strain currently circulating in South America). We will then determine how the virus population changes as it passes through important tissue/compartments within each mosquito, including midguts, hemolymph, salivary glands and saliva. This aspect of the proposal is based on our ongoing work with West Nile virus and published literature on Chikungunya virus. The second aim is to assess how temperature influences virus mutational diversity during mosquito infection. This is a frequently asked, but never adequately answered question. Together, these aims will permit us to draw linkages across virus-vector systems and to provide predictions regarding likely adaptive mutations to the ZIKV genome that may permit more rapid spread in the Americas. The proposed research leverages extensive experience in virus-vector interactions, NGS and computational biology and a large amount of preliminary data on the WNV-Culex system.

这一提议是为了一个新的R21，预测寨卡病毒出现的遗传决定因素。该项目旨在 采取积极主动的方法来评估寨卡病毒如何适应美国媒介。最终，这项研究将 有助于扩大PI实验室中关于特定， 生态相关载体和宿主对虫媒病毒适应度决定因素和种群遗传学的影响。特别是， 在本项目中，我们将确定如何感染Ae。埃及伊蚊Ae. albopictus和Cx.致倦症影响 ZIKV基因。我们还将评估环境温度在形成病毒种群中的作用。 目标1的重点是表征来自美洲的蚊子品系的媒介能力， ZIKV的亚洲谱系（即目前在南美洲流行的毒株）。然后我们将决定如何 病毒群体随着其通过每只蚊子内的重要组织/隔室而变化， 包括中肠、血淋巴、唾液腺和唾液。这方面的建议是基于我们正在进行的 研究西尼罗河病毒并发表关于基孔肯雅病毒的文献。第二个目标是评估如何 温度影响蚊子感染期间病毒的突变多样性。这是一个经常被问到的问题，但是 从来没有充分回答的问题。 总之，这些目标将使我们能够在病毒载体系统之间建立联系，并提供预测 关于ZIKV基因组可能的适应性突变，这可能允许在美洲更快地传播。 拟议的研究利用了病毒-载体相互作用，NGS和计算方面的丰富经验。 生物学和大量关于WNV-库蚊系统的初步数据。