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.

该提案针对新的 R21，预测寨卡病毒出现的遗传决定因素。 采取积极主动的方法来评估寨卡病毒如何适应美国媒介。 为 PI 实验室中有关特定、 虫媒病毒适应性决定因素和群体遗传学的生态相关载体和宿主。 在这个项目中，我们将确定埃及伊蚊、白纹伊蚊和致倦库蚊的感染如何影响。 我们还将评估环境温度在病毒种群形成中的作用。 目标 1 侧重于表征源自美洲的蚊子品系的媒介能力 然后我们将确定 ZIKV 的亚洲谱系（即目前在南美流行的病毒株）。 当病毒通过每只蚊子内的重要组织/隔室时，病毒数量会发生变化， 包括中肠、血淋巴、唾液腺和唾液。这方面的提案是基于我们正在进行的。 与西尼罗河病毒合作并发表有关基孔肯雅病毒的文献第二个目标是评估如何进行。 温度影响蚊子感染过程中的病毒突变多样性这是一个经常被问到的问题。 从未充分回答问题。 总之，这些目标将使我们能够建立病毒载体系统之间的联系并提供预测 关于 ZIKV 基因组可能发生的适应性突变可能会导致在美洲更快地传播。 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 生物学和大量关于西尼罗河病毒-库蚊系统的初步数据。