Genetic signatures of dengue virus emergence

登革热病毒出现的遗传特征

• 批准号: 8378782
• 负责人: SHANNON N BENNETT
• 金额: $ 25.2万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8378782
• 关键词: Animal Model; Asia; Avian Influenza; Biological Assay; Categories; Communicable Diseases; Dengue; Dengue Virus; Disease; Disease Outbreaks; Emerging Communicable Diseases; Epidemic; Evolution; Experimental Models; Genetic; Goals; HIV; Hawaii; Human; Infectious Diseases Research; Mutation; Pathogenesis; Phase; Phenotype; Population; Puerto Rico; Relative (related person); Research; Role; Severe Acute Respiratory Syndrome; Severities; Texas; Tissue Model; United States; Virus; West Nile virus; biodefense; comparative; demographics; in vitro Model; in vivo Model; sample fixation; transmission process; vector; vector mosquito; virus genetics

Dengue (DENV) has re-emerged in the last 25 years as one of the most significant emerging infectious diseases worldwide, posing a significant category A biodefense threat to the United States with ongoing epidemics in Puerto Rico, and recent outbreaks in Hawaii (2001) and Texas (1999, 2005, 2006). Its global resurgence, while partly explained by changing human demographics, increasing hyperendemicity, and mosquito vector expansions, remains poorly understood, especially with respect to the importance of virus evolution. We fill this critical gap by conducting a comparative evolutionary examination of DENV strains undergoing epidemic expansion, from replicate populations across the Asia-Pacific arena, paired with directed tissue and animal model assays for changes in virus phenotype related to epidemics. Our long-term goal is to resolve how viral genetic change drives disease emergence. The objective of the proposed research is to characterize evolution in dengue viruses isolated from epidemics relative to their endemic forms and confirm the impact of genetic changes in experimental models, the rationale being that identification of such viral genetic changes and their mechanisms of fixation will illuminate determinants of dengue epidemic potential and ultimately pathogenesis. Specific Aim 1: Determine the evolution of DENV between endemic and epidemic transmission phases to identify synapomorphies of higher epidemic potential. Specific Aim 2: Confirm the relationship between genetic changes in DENV epidemic strains and their phenotypic effects in in vitro models. Specific Aim 3: Confirm the relationship between genetic changes in DENV epidemic strains and their phenotypic effects in in vivo models

登革热（DENV）在过去25年中再次出现，成为最重要的新发传染病之一