Temperature dependent impacts of RNA virus population evolution

RNA 病毒种群进化的温度依赖性影响

• 批准号: 9755359
• 负责人: Reyes Murrieta
• 金额: $ 3.57万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9755359
• 关键词: Aedes; Alphavirus; Arbovirus Infections; Arboviruses; Area; Arthropods; Chikungunya virus; Colorado; Competence; Consensus; Consensus Sequence; Culex (Genus); Culicidae; Dengue Virus; Disease; Disease Outbreaks; Environment; Evolution; Flaviviridae; Flavivirus; Genetic Variation; Genome; Genotype; Haplotypes; Hemolymph; High temperature of physical object; In Vitro; Infection; Lead; Literature; Midgut; Modeling; Mosquito Control; Mutation; Nature; Nucleotides; Outcome Study; Phenotype; Play; Population; Population Genetics; Population Heterogeneity; Process; Public Health; RNA Viruses; Rift Valley fever virus; Role; Saliva; Site; St. Louis Encephalitis Virus; Temperature; Testing; Tissues; Togaviridae; Variant; Venezuelan Equine Encephalitis Virus; Vertebrates; Viral; Virus; West Nile viral infection; West Nile virus; Western Equine Encephalitis Virus; Yellow fever virus; Zika Virus; climate change; climate data; combat; fitness; follow-up; genetic analysis; global health; in vivo; insight; mutant; novel virus; pathogen; predictive modeling; response; transcriptome sequencing; vector; viral transmission; virus genetics

Abstract The emergence of arthropod-borne viruses (arboviruses) is an ongoing public health concern. The conditions that lead to the emergence of new virus genotypes are poorly understood. In mosquitoes, temperature profoundly impacts virus transmission via replication rate and the likelihood that virus will disseminate from the midgut and ultimately be transmitted. Yet, there is a gap in the literature on the effect that extrinsic incubation (EI) temperature has on virus diversification in the mosquito. Therefore, we plan to study the role that temperature plays in arbovirus evolution during the EI period. First, we will determine the extent to which EI temperature impacts Zika virus (ZIKV) and West Nile virus (WNV) vector competence in Aedes and Culex mosquitoes respectively, and following this use RNA-seq to identify how the consensus genome changes in response to the temperature of EI. Next, we will assess temperature driven single-nucleotide variants and conduct population genetics analysis to determine the extent of the EI temperature’s effect on viral population diversity. This may provide a temperature specific model of viral evolution. Last, we will validate our temperature driven, viral evolution model by comparing it to locally transmitted WNV field isolates. The outcome of these studies will provide insight to arbovirus evolution and potentially be used to predict environmental conditions that may lead to evolution and selection of novel virus genotypes that cause severe outbreaks. Hypothesis: We hypothesis that when arboviruses such as WNV and ZIKV undergo extrinsic incubation in their respective vector, a high temperature of incubation drives viral population diversity, leading to mutant haplotypes being transmitted. This hypothesis will be tested in three specific aims Aim 1. Determine the extent in which the temperature of extrinsic incubation impacts ZIKV and WNV vector competence in mosquitoes and identify any temperature driven consistent and predictable consensus genome changes. Aim 2. Determine how the temperature of extrinsic incubation influences ZIKV and WNV population diversity within mosquitoes. Aim 3. Characterize the effects of temperature on WNV evolution in Fort Collins from 2013-2017.

抽象的 节肢动物传播的病毒（虫媒病毒）的出现是一个持续的公共卫生问题。条件 人们对导致新病毒基因型出现的原因知之甚少。对于蚊子来说，温度 通过复制率和病毒从传播途径传播的可能性深刻影响病毒传播 中肠并最终被传播。然而，关于外部孵化的影响的文献还存在空白。 （EI）温度对蚊子体内病毒的多样化有影响。因此，我们计划研究以下角色： EI 期间温度在虫媒病毒的进化中发挥着作用。首先，我们将确定 EI 的程度 温度影响伊蚊和库蚊中寨卡病毒（ZIKV）和西尼罗河病毒（WNV）载体的能力 分别蚊子，然后使用 RNA-seq 来识别共有基因组如何变化 对 EI 温度的响应。接下来，我们将评估温度驱动的单核苷酸变异和 进行群体遗传学分析以确定 EI 温度对病毒群体的影响程度 多样性。这可能提供病毒进化的温度特定模型。最后，我们将验证我们的 通过将其与本地传播的西尼罗河病毒野外分离株进行比较，建立了温度驱动的病毒进化模型。这 这些研究的结果将为虫媒病毒的进化提供见解，并有可能用于预测 可能导致新病毒基因型进化和选择的环境条件，导致严重的后果 爆发。 假设：我们假设当 WNV 和 ZIKV 等虫媒病毒在体外进行孵化时， 它们各自的载体，高温孵化会驱动病毒种群多样性，导致突变体 单倍型正在传播。该假设将在三个具体目标上进行检验 目标 1. 确定外源孵化温度对 ZIKV 和 WNV 载体的影响程度 蚊子的能力并识别任何温度驱动的一致且可预测的共识基因组 变化。 目标 2. 确定外部孵化温度如何影响 ZIKV 和 WNV 种群多样性 蚊子之内。 目标 3. 描述 2013-2017 年柯林斯堡温度对 WNV 演变的影响。