Predicting genetic determinants of Zika virus emergence

这项建议是为了建立一个新的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评估寨卡病毒可能如何适应美国的媒介。最终，这项研究将 有助于在PI的实验室中扩大关于特定、 虫媒病毒适合性决定因素和种群遗传学上的生态相关载体和宿主。特别是， 在这个项目中，我们将确定Ae的感染方式。Ae.埃及伊格普提Albopictus和Cx.Ququiefasciatus的影响 ZIKV遗传学。我们还将评估环境温度在塑造病毒种群方面的作用。 目标1重点是描述起源于美洲的蚊子品系的媒介能力 ZIKV的亚洲血统(即目前在南美洲流行的毒株)。然后我们将确定如何 病毒种群在通过每只蚊子体内的重要组织/隔间时会发生变化， 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 研究西尼罗河病毒并出版有关基孔肯雅病毒的文献。第二个目标是评估如何 在蚊子感染期间，温度会影响病毒的变异多样性。这是一个经常被问到的问题，但 从来没有充分回答过这个问题。 总之，这些目标将使我们能够在病毒媒介系统之间建立联系，并提供预测 关于ZIKV基因组可能的适应性突变，这可能会使其在美洲更迅速地传播。 拟议的研究利用了病毒-媒介相互作用、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-库雷克斯系统的初步数据。

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.