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.

莱姆病曾经仅限于北大西洋沿岸和选定的中西部北部社区， 但在过去二十年里，这种人畜共患疾病的分布和流行范围大大扩大。这 莱姆病媒介的攻击性人类叮咬鹿蜱媒介首次被识别为 1997 年保持了波瓦桑病毒 (POW) 的独特谱系，但人类脑炎病例 直到 2006 年才认识到“鹿蜱病毒”所致。严重的神经系统疾病是该病的一个标志 直到最近，经典波瓦桑热在莱姆病流行地区的居民中仍然很少见。 现在越来越多地报道由波瓦桑病毒引起的脑炎病例 英格兰和中西部北部。最近出现的战俘人畜共患的生物学基础 需要分析。欧亚蜱传脑炎病毒复合体 (TBEV) 包含多种病毒 物种（包括战俘）、亚型和地理隔离群，其导致人类死亡的能力各不相同 疾病，并且有大量关于遗传、表型和临床变异的文献 欧亚 TBEV 的特征应指导我们分析潜在的公共卫生负担 北美的战俘。我们最重要的假设是波瓦桑病毒，就像 TBEV 还包括具有不同能力的谱系、基因型或群体 引起人类疾病。我们建议使用我们现有的地理隔离区来检验这一假设 战俘以及我们将收集的其他分离株，因为它们具有引起神经系统疾病的能力 使用已发表的 TBEV 神经趋向性小鼠模型。此外，可能某些血统， 人类咬鹿蜱可以更有效地传播战俘的基因型或群体 莱姆病的媒介，这有助于解释新出现的流行病学情况。因此， 我们还将确定地理隔离株的感染能力和被感染能力是否可能不同 通过蜱传播。最后，我们将应用全基因组测序的强大工具 分析 Powassan 病毒的种群结构并确定其任何遗传相关性 神经营养能力。综合起来，这些观察结果可能有助于解释这一变化 一种虫媒病毒的流行病学，该病毒在莱姆病中悄然流行了二十多年 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 Powassan 遗传多样性的病理生物学相关性，我们可以更好地定义蜱的潜力 传染性脑炎继续成为北美的公共卫生负担。