Molecular bases of tick-borne flavivirus transmission

蜱传脑炎病毒（TBEV）每年在欧洲和亚洲的森林地区引起流行规模的蜱传脑炎（TBE）人间感染。人们的疾病症状差别很大，包括无症状感染、严重但可恢复的发烧、脑膜脑炎、使人衰弱或致命的脑炎以及缓慢发展（数年）的进行性脑炎。其原因尚不清楚，尽管已观察到在不同地区传播的个别TBEV毒株的毒性与疾病的严重程度之间存在某种相关性。远东地区的人类感染最为严重，经常涉及中枢神经系统，占死亡人数的20-40%。西伯利亚的乙脑通常伴有较轻的疾病（占病死率的7-8%），但慢性疾病更为常见（1-3%）。与西欧TBEV病毒株相关的感染导致的死亡率不到2%。虽然造成这些差异的原因尚不清楚，但我们的初步研究表明，TBEV意外逃逸到新的蜱虫物种中可能需要病毒改变其基因组的某些部分，以加速病毒在新蜱虫物种中的复制，从而促进病毒在自然界中的传播。然而，这些有利于病毒的基因变化可能会增加TBEV的毒性，因此对人类不利。基因更新的毒性更强的病毒的传播可能确实是人类流行病的原因。在这个项目中，我们建议研究两种不同的TBEV菌株，一种称为Hypr，对蓖麻I.和另一种称为v .对过sulcatus的适应，是由TBEV基因组的哪个部分负责的。这些病毒不能在外星人体内复制。蜱的种类和它们对人类的致病特性也不同；v是从发烧恢复的患者中分离出来的，而Hypr与TBE的致命病例有关。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，来确定决定蜱虫传播模式的病毒基因组部分与决定TBEV毒力特性的病毒基因组部分之间是否存在相关性。这项研究有助于我们理解环境中新病原体出现的机制，并将有助于设计适当的策略来干预感染。

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.