Development of a Tick Transmission Model for Heartland Virus Pathogenesis

 描述（由申请方提供）：最近在美国报告了一种与严重发热性疾病相关的新型蜱传病毒，Heartland病毒（HLV）。HLV与严重发热伴血小板减少综合征病毒（SFTSV）密切相关，SFTSV是一种蜱传播病毒，病死率高达30%，与黄热病、拉沙热、汉坦病毒肺综合征、克里米亚-刚果出血热和未经治疗的落基山斑疹热相当。由于HLV在美国是一种新描述的病毒，其感染发生率、疾病严重程度范围和发病机制目前尚不清楚。到目前为止，已报告6例人间病例，其中1例死亡。缺乏动物模型是理解HLV感染的发病机制和宿主免疫应答的关键障碍，也阻碍了预防和控制HLV感染的工具的开发。这项研究具有创新性，因为它是第一个通过受感染的蜱叮咬开发HLV感染的动物模型，并且对新发现的人类病原体具有快速反应。这项研究将对美国的公共卫生产生影响，并将进一步推进我们目前对HLV感染和可能的SFTSV感染的理解。

 DESCRIPTION (provided by applicant): A new tick-borne virus, Heartland virus (HLV), associated with severe febrile illness has recently been reported in the US. HLV is closely related to the severe fever with thrombocytopenia syndrome virus (SFTSV), a tick transmitted virus, with a case fatality rate as high as 30%, putting it on par with yellow fever, Lassa fever, hantavirus pulmonary syndrome, Crimean-Congo hemorrhagic fever, and untreated Rocky Mountain spotted fever. As HLV is a newly described virus in the US, its the incidence of infection, range of disease severity and pathogenesis are currently unknown. So far, 6 human cases have been reported with one fatal case. Lack of an animal model is a critical barrier to understand the pathogenesis and host immune response to HLV infection, and also impedes development of tools for prevention and control of HLV infection. The proposed study is innovative in that it is the first to develop an animal model for HLV infection by infected tick bites, and also in its rapid response to a newly identified human pathogen. This study will have an impact on US public health, and will further advance our current understanding of HLV infection and probably SFTSV infection as well.