Molecular bases of tick-borne flavivirus transmission

蜱传黄病毒传播的分子基础

• 批准号: G0801208/1
• 负责人: Tamara Gritsun
• 金额: $ 51.37万
• 依托单位: University of Reading
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0801208%2F1
• 关键词: Molecular; bases; tick; borne; flavivirus

The tick-borne encephalitis virus (TBEV) causes annual human infections of tick-borne encephalitis (TBE) at the epidemic scale in forested regions of Europe and Asia. The disease symptoms in people are significantly varied and include asymptomatic infections, severe although recoverable fevers, meningoencephalitis, debilitating or fatal encephalitis and slow developing (for years) progressive encephalitis. The reasons for that are not known although some correlation between the virulent properties of individual strains of TBEV that circulate in different regions and severity of the disease has been observed. Human infections in Far Eastern Asia are the most severe with frequent involvement of the CNS and 20-40% of fatality. TBE in Siberia is usually associated with a less severe disease (7-8% of fatality) but chronic disease is observed more frequently (1-3%). Infections linked to West European strains of the TBEV cause a fatality rate less than 2%. Although the reasons for these differences are not clear, our preliminary research suggests that accidental escape of TBEV into a new tick species might demand the virus to change certain parts of their genome, to speed up virus replication in new tick species and thereby facilitate the virus spread in nature. However these genetic changes, working tothe virus s advantage, might increase the virulent properties of the TBEV and therefore be disadvantageous for humans. The spread of genetically-renewed more virulent TBEV might indeed be the reason for the human epidemics. In this project we suggest to investigate which parts of the TBEV genome are responsible for the adaptation of two different TBEV strains, one called Hypr, to tick I. ricinus and the other, Vs to I. persulcatus. These viruses cannot replicate in ?alien? tick species and they are also different in their pathogenic properties in humans; the Vs was isolated from the patient that recovered from the fever whereas Hypr was associated with fatal case of the TBE. We will use a state of art new molecular technologies such as genetic engineering and DNA microarray analysis to establish whether or not there is a correlation between the parts of the virus genome that determine tick-transmission pattern and those that determine virulent properties of the TBEV. This research contributes to our understanding of the mechanisms of emerging of new pathogens in the environment and will facilitate the design the appropriate strategy to intervene with infections.

蜱传脑炎病毒(TBEV)在欧洲和亚洲的森林地区每年都会造成流行规模的森林脑炎(TBE)的人类感染。人们的疾病症状有很大的不同，包括无症状的感染，虽然可以恢复的严重发烧，脑膜脑炎，衰弱或致命的脑炎，以及缓慢发展(多年)的进行性脑炎。其原因尚不清楚，尽管已经观察到在不同地区传播的TBEV个别毒株的毒力特性与疾病严重程度之间的一些相关性。远东地区的人类感染最为严重，常累及中枢神经系统，致死率为20-40%。在西伯利亚，TBE通常与不太严重的疾病(7-8%的死亡率)有关，但慢性病更常见(1-3%)。与西欧TBEV毒株有关的感染导致的死亡率不到2%。虽然这些差异的原因尚不清楚，但我们的初步研究表明，TBEV意外逃逸到一个新的扁虱物种可能需要病毒改变其基因组的某些部分，以加快病毒在新的扁虱物种中的复制，从而促进病毒在自然界的传播。然而，这些基因变化，发挥了S病毒的优势，可能会增加TBEV的毒力特性，因此对人类不利。基因更新的更强毒力的TBEV的传播可能确实是人类流行的原因。在这个项目中，我们建议调查TBEV基因组的哪些部分负责两种不同的TBEV毒株的适应，一种称为Hypr，对蓖麻黄单胞菌的适应，另一种，VS对全沟单胞菌的适应。这些病毒不能在外星人体内复制？在人类中，它们的致病特性也不同；VS是从发烧康复的患者身上分离出来的，而Hypr与致命的TBE病例有关。我们将使用最先进的新分子技术，如基因工程和DNA微阵列分析，以确定决定扁虱传播模式的病毒基因组部分与决定TBEV毒力特性的部分之间是否存在相关性。这项研究有助于我们理解新病原体在环境中出现的机制，并将有助于设计适当的策略来干预感染。