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Emergence of tick borne encephalitis in North America

北美出现蜱传脑炎

基本信息

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
项目类别：
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

项目摘要

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.

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