Vector competence for TBEV replication limiting viral spread (VECTORS)

蜱传脑炎病毒（TBEV）是人类和动物中的一种新兴病原体，分布在从日本到整个亚洲到欧洲的广泛地理范围内。在过去的几十年中，人畜共患TBEV感染的发病率在许多流行国家急剧上升，例如在德国几乎增加了六倍，尽管德国各地区的总体增长水平差异很大：TBEV存在于德国东部和南部，但没有证据表明其在该国最西部地区传播。同样，在荷兰的人类和动物中也没有发现TBEV的传播。这种中断TBEV流行背后的原因在很大程度上仍然未知。TBEV生命周期的一个主要组成部分是它在I.蓖麻，它的主要蜱媒介。我们假设，与优先项目生态学和新出现病毒性疾病的物种障碍SPP 1596的总体目标一致，I. TBEV感染的内在易感性、共食行为、TBEV跨stadial传播能力、微生物组及其动态等是TBEV流行的决定因素。VECTORS旨在将基础和最先进的分子病毒学和微生物学与无脊椎动物载体生物学和生态学联系起来。具体目标是：1）确定源自德国东部地方病与西部非地方病地区的假定分界线以东和以西不同位置的蓖麻硬蜱感染TBEV的能力，以及能够通过共同喂养和/或通过跨场感染传播TBEV的能力。2)评估蓖麻I.亚群的微生物组对其TBEV复制能力的影响。为此，将从德国和沿着德国-荷兰边境的地方病和非地方病地区采集蜱虫，以确定相应三个蜱虫阶段的感染和非感染种群的时空分布及其可能的重叠。将分离TBEV循环菌株并用于产生分子克隆，其将用于实验感染和TBEV蜱共喂养和跨场传播实验。收集的蜱虫也将用于确定它们的微生物组，在未感染和抗生素治疗的蜱虫中进行实验性TBEV感染，将评估它们对TBEV复制能力的潜在影响。收集到的数据将为基于科学的风险评估奠定基础，该评估涉及德国和欧洲目前流行和未开发地区TBEV感染强度和传播的未来增加。

Tick-borne encephalitis virus (TBEV) is an emerging pathogen in humans and animals, ranging over a wide geographical range spanning from Japan, throughout Asia into Europe. The incidence of zoonotic TBEV infections has risen dramatically in many endemic countries during the past decades, having for example increased almost six-fold in Germany, although the overall level of increase varies considerably across German regions: TBEV is present in eastern and southern Germany, but there is no evidence for its circulation in the most western part of the country. Likewise, no TBEV circulation has been found in The Netherlands in humans and animals. The reasons behind this interrupted TBEV prevalence remain largely unknown. A major component of the TBEV life cycle is its replication in I. ricinus, its major tick vector. We hypothesize, in line with the overall aim of the Priority Program Ecology and species barriers in Emerging Viral Diseases SPP1596, that biological traits of I. ricinus, such as intrinsic susceptibility to TBEV infection, co-feeding behaviour, ability for trans-stadial TBEV transmission, microbiome, and dynamics of these, are determinants of TBEV endemicity. VECTORS aims at linking basic and state-of-the-art molecular virology and microbiology to invertebrate vector biology and ecology. The specific objectives are to: 1) Determine the ability of I.ricinus ticks originating from different locations east and west of a postulated demarcation line separating eastern endemic from western non-endemic areas in Germany to be infected with, and capable to transmit TBEV via co-feeding and/or via trans-stadial infection. 2) Assess the influence of the microbiome of I.ricinus subpopulations on their TBEV replication competence. To this end ticks will be collected from endemic and non-endemic areas in Germany and along the German-Dutch border to determine the spatio-temporal distribution of infected and non-infected populations of the respective three tick stages, and their possible overlaps. TBEV circulating strains will be isolated and used for the generation of molecular clones, which will be used for experimental infection and TBEV tick co-feeding and trans-stadial transmission experiments. Collected ticks will also be used to determine their microbiomes, and experimental TBEV infections in naïve and antibiotics treated ticks, will assess their potential impact on TBEV replication competence. The collected data will form the basis for a science-based risk assessment concerning the future increase in intensity and spread of TBEV infections in currently endemic and virgin areas in Germany and Europe.