Reassortment of Bunyavirus in ticks and animal models

蜱和动物模型中布尼亚病毒的重排

基本信息

批准号：
10512873
负责人：
Jae U Jung
金额：
$ 59.31万
依托单位：
CLEVELAND CLINIC LERNER COM-CWRU
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-19 至 2027-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10512873
关键词：
4 year old Affect Age Animal Model Animals Antigenic Variation Arboviruses Attenuated Live Virus Vaccine Basic Science Biological Assay Blood CNR1 gene Cell Culture Techniques Cells Characteristics Clinical Communicable Diseases Coxiella DNA Vaccines Dangerousness Disease Disease Outbreaks Emergency Situation Epidemic Far East Fatality rate Female Ferrets Fever Future Genes Genetic Genetic Processes Genetic Recombination Genome Genotype Glycoproteins Goals Heartland virus Human IFNAR1 gene Immunocompetent In Vitro Infection Interferons Larva Mammals Mediating Methods Midgut Modeling Mus Nature Nymph Orthobunyavirus Ovary Pathogenesis Pathogenicity Patients Phenotype RNA RNA Viruses Risk Factors Role Salivary Salivary Glands Severe Fever with Thrombocytopenia Syndrome Virus Symptoms Syndrome System Testing Thrombocytopenia Ticks Time Viral Viral Pathogenesis Virus Virus Diseases Virus-like particle age related aged base climate change clinical application clinical diagnosis co-infection egg feeding fitness immunogenicity in vivo insight mortality mouse model neutralizing antibody novel older patient pathogen pathogenic virus reverse genetics symbiont tick feeding tick-borne tool transmission process vector viral fitness

项目摘要

Project Summary/Abstract Listed in the WHO top nine most dangerous pathogens, SFTSV has 12-30% fatality rates, rapidly spreads through tick-to-animal/human, human-to-human and animal-to-human and induces immunopathogenic disease with a characteristic thrombocytopenia. Virus reassortment is a process of genetic recombination that is exclusive to segmented RNA viruses in which co-infection of a cell of natural host and vector with multiple viruses may result in the shuffling of gene segments to generate progeny viruses with novel genome combinations. Reassortment greatly affects virus fitness and directly influences antigenic variation, confounding available methods of virus control. In this application, we will test the hypothesis that tick-mediated natural course of SFTSV infection and reassortment introduces phenotypic changes of fitness, transmissibility, antigenicity, or pathogenicity into progeny reassortants. The goal of this study is to demonstrate the natural course of SFTSV infection and reassortment for fitness, immunogenicity, transmissibility, and pathogenesis in in vitro and in vivo animal models and H. longicornis ticks, ultimately bridging basic research to clinical application.

项目概要/摘要 SFTSV 被世界卫生组织列为九大最危险病原体，其死亡率为 12-30%，且死亡率迅速上升通过蜱传动物/人、人传人以及动物传人，并诱发具有特征性血小板减少症的免疫致病性疾病。病毒重组是一个过程分段RNA病毒独有的基因重组，其中细胞共感染天然宿主和载体与多种病毒的混合可能会导致基因片段的改组产生具有新基因组组合的子代病毒。重组对病毒影响很大适应性并直接影响抗原变异，混淆了现有的病毒控制方法。在在本申请中，我们将测试蜱介导的 SFTSV 感染自然过程的假设，以及重配引入了适应性、传染性、抗原性或致病性的表型变化进入后代重配体。本研究的目的是证明 SFTSV 的自然过程体外感染和重组的适应性、免疫原性、传播性和发病机制以及体内动物模型和长角蜱，最终将基础研究与临床联系起来应用。