Emergence of tick borne encephalitis in North America

北美出现蜱传脑炎

• 批准号: 10063475
• 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/10063475
• 关键词: Address; Anaplasmosis; Arbovirus Infections; Arboviruses; Babesiosis; Biological; Borrelia miyamotoi; Characteristics; Clinical; Communities; Companions; Complex; Deer; Deer Tick; 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-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选定的上中西部社区， 但这种人畜共患病的分布和流行在过去20年中大大扩大。的 莱姆病病原体的攻击性人咬鹿蜱媒介首次被确认， 在1997年，人类脑炎病例保持了Powassan病毒（POW）的独特谱系， 仅在2006年才认识到可归因于“鹿蜱病毒”。严重的神经系统疾病， 经典的波瓦桑热，仍然罕见的莱姆病流行的居民，直到最近。 由于Powassan病毒引起的脑炎病例现在越来越多地报告， 英格兰和上中西部。最近人畜共患战俘出现的生物学基础 需要分析。欧亚蜱传脑炎病毒复合体（TBEV）包括多种 种（包括POW）、亚型和地理分离株，其引起人类感染的能力不同 疾病，并且有丰富的文献涉及遗传、表型和临床 欧亚TBEV的特征应该指导我们分析潜在的公共卫生负担 北美的战俘。我们的假设过于牵强， TBEV还包括能力不同的谱系、基因型或群体， 导致人类疾病。我们建议使用我们现有的地理分离株来检验这一假设 POW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嗜神经性小鼠模型。此外，可能是某些血统， POW的基因型或种群更有效地通过人咬鹿蜱传播 莱姆病的传播媒介，这有助于解释新出现的流行病学情况。因此，委员会认为， 我们还将确定地理分离株的感染能力是否不同， 通过蜱虫传播最后，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，并确定任何遗传相关性， 亲神经能力综合起来，这些观察结果可能有助于解释 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，但现在显然是一种新兴的人畜共患病。最终，通过描述 病理生物学相关的Powassan遗传多样性，我们可以更好地定义蜱的潜力， 传播性脑炎继续成为北美公共卫生负担。