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; 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.

该建议是针对新的R21的，可预测寨卡病毒出现的遗传决定因素。这个项目旨在 采取积极的方法来评估寨卡如何适应美国媒介。最终，这项研究将 在PI实验室中有关特定的影响， 关于arbovirus适应性的生态相关载体和宿主决定了种群遗传学。尤其， 在这个项目中，我们将确定AE感染的方式。埃及，ae。白化病和CX。 Quinquefasciatus的影响 ZIKV遗传学。我们还将评估环境温度在塑造病毒种群中的作用。 AIM 1专注于表征源自美洲的蚊子菌株的矢量能力 ZIKV的亚洲血统（即目前在南美洲流通的菌株）。然后，我们将确定如何 病毒种群通过每个蚊子内的重要组织/室时变化， 包括中肠，血淋巴，唾液腺和唾液。该提案的这一方面是基于我们正在进行的 与西尼罗河病毒合作，并出版有关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突变多样性。这是一个经常询问的，但是 从来没有充分回答问题。 这些目标共同使我们能够跨病毒媒介系统建立联系并提供预测 关于可能对ZIKV基因组的适应性突变，这可能会使美洲更快地传播。 拟议的研究利用了病毒矢量相互作用，NGS和计算方面的丰富经验 生物学和有关WNV-Culex系统的大量初步数据。