Emergence of tick borne encephalitis in North America

北美出现蜱传脑炎

• 批准号: 10312001
• 负责人: Gregory David Ebel
• 金额: $ 49.96万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-12-12 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10312001
• 关键词: Address; Anaplasmosis; Arbovirus Infections; Arboviruses; Babesiosis; Biological; Black-legged Tick; Borrelia miyamotoi; Characteristics; Clinical; Communities; Companions; Complex; Deer; Disease; Encephalitis; Endemic Diseases; Epidemiology; Exposure to; Fever; Flavivirus; Genetic; Genetic Variation; Genotype; Geography; Human; Infection; Invaded; Literature; Locales; Lyme Disease; Midwestern United States; Nature; Nervous system structure; Neurotropism; New England; North America; Outcome; Pathogenesis; Pathology; Phenotype; Population; Powassan encephalitis; Powassan virus; Prevalence; Process; Public Health; Publishing; Reporting; Research; Risk; Site; Structure; Testing; Tick Infestations; Tick-Borne Encephalitis; Tick-Borne Encephalitis Virus; Ticks; Variant; Viral; Virus; Virus Diseases; Zoonoses; disorder risk; enzootic; genome sequencing; human disease; mouse model; nervous system disorder; neurotropic; pathogen; tick transmission; tool; transmission process; vaccine development; vector tick; virus genetics; whole genome

Lyme disease was once restricted to coastal North Atlantic and selected Upper Midwest communities, but the distribution and prevalence of this zoonosis has greatly expanded in the last two decades. The aggressively human biting deer tick vector of the agent of Lyme disease was first recognized to maintain a distinct lineage of Powassan virus (POW) in 1997, but human encephalitis cases attributable to “deer tick virus” was recognized only in 2006. Severe neurologic disease, a hallmark of classical Powassan fever, remained rare in residents of Lyme-endemic sites until recently. Encephalitis cases attributed to Powassan virus are now being increasingly reported from New England and the upper Midwest. The biological basis for the recent zoonotic emergence of POW requires analysis. The Eurasian tick borne encephalitis virus complex (TBEV) comprises diverse species (including POW), subtypes and geographic isolates that vary in their capacity to cause human disease, and there is a rich literature concerning variation in the genetic, phenotypic and clinical characteristics of Eurasian TBEV that should guide our analysis of the potential public health burden of POW in North America. Our overaraching hypothesis is that Powassan virus, like TBEV, also comprises lineages, genotypes, or populations that differ in capacity to cause human disease. We propose to test this hypothesis using our existing geographic isolates of POW as well as additional isolates that we shall collect for their capacity to cause neurologic disease using a published mouse model for TBEV neurotropism. In addition, it may be that certain lineages, genotypes, or populations of POW are more efficiently transmitted by the human biting deer tick vector of Lyme disease, and this helps to explain the emerging epidemiological situation. Accordingly, we shall also determine whether geographic isolates may differ in their capacity to infect and be transmitted by ticks. Finally, we shall apply the powerful tools of whole genome sequencing to analyze the population structure of Powassan virus as well as identify any genetic correlates of neurotropic capacity. Taken together, these observations may help explain the changing epidemiology of an arbovirus that has been silently enzootic for over 2 decades in Lyme disease endemic sites, but is now apparently an emerging zoonosis. Ultimately, by describing the pathobiological correlates of Powassan genetic diversity, we can better define the potential for tick borne encephalitis to continue to emerge as a public health burden in North America.

莱姆病一度仅限于北大西洋沿岸和部分中西部地区， 但在过去的20年里，这种人畜共患病的分布和流行范围已经大大扩大。这个 首次发现莱姆病病原体的侵袭性人类咬人鹿虱媒介 在1997年保持了波瓦桑病毒(POW)的独特谱系，但人类脑炎病例 可归因于“鹿虱病毒”的疾病直到2006年才被发现。严重的神经系统疾病，这是一个标志 直到最近，在莱姆病流行地区的居民中，典型的鲍瓦桑热仍然很少见。 被归因于鲍瓦桑病毒的脑炎病例现在从纽约报告越来越多 英格兰和中西部北部。战俘最近出现人畜共患病的生物学基础 需要分析。欧亚硬蜱传播的脑炎病毒复合体(TBEV)由不同的 引起人类感染能力不同的物种(包括战俘)、亚型和地理分离株 疾病，并且有丰富的关于遗传、表型和临床变异的文献 欧亚TBEV的特征应该指导我们对潜在的公共卫生负担的分析 在北美的战俘。我们过分夸张的假设是，鲍瓦桑病毒，就像 TBEV，也包括在能力上不同的血统、基因类型或群体 导致人类疾病。我们建议使用我们现有的地理隔离来验证这一假设 战俘和其他分离株，我们将收集它们导致神经系统疾病的能力 使用已发表的TBEV神经趋向性的小鼠模型。此外，可能是某些血统， 战俘的基因类型或种群通过人类咬人的鹿虱传播更有效 莱姆病的病媒，这有助于解释新出现的流行病学情况。因此， 我们还将确定地理分离株感染和感染的能力是否会有所不同 由扁虱传播的。最后，我们将应用全基因组测序的强大工具来 分析鲍瓦桑病毒的种群结构，并确定与 嗜神经能力。综上所述，这些观察结果可能有助于解释这种变化 一种在莱姆病中沉默流行了20多年的虫媒病毒的流行病学 地方病流行地点，但现在显然是一种新出现的人畜共患病。最终，通过描述 鲍瓦桑基因多样性的病理生物学相关性，我们可以更好地定义扁虱的潜在可能性 经传播的脑炎在北美继续成为公共卫生负担。