Influence of the interferon system to control tick-transmitted Bourbon virus

干扰素系统对控制蜱传波旁病毒的影响

• 批准号: 407503227
• 负责人: Professor Dr. Georg Kochs
• 金额: --
• 依托单位: Institut für Virologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/407503227?language=en
• 关键词: Influence; interferon; system; control; tick

Bourbon virus belongs to the Thogotovirus genus within the family of orthomyxoviruses. Thogotoviruses were isolated from ticks in Africa, Asia and South Europe and are known to cause severe diseases in farm animals but only rarely in humans. Therefore, the recent isolation of a new Thogotovirus, designated Bourbon virus, from a fatal case in the USA, who suffered from a severe febrile disease and died from multi organ failure, was surprising. The mechanisms that caused this severe disease outcome is unknown but potentially linked to an unexpected virulence of the Bourbon virus or defects in the host innate immune response.To provide evidence for these hypotheses we want to study the impact of the interferon system on the pathogenic potential of Bourbon virus in vitro and in a suitable mouse model. Moreover, we want to identify molecular determinants explaining the interferon sensitivity of this newly emerging Thogotovirus. In contrast to other Thogotoviruses, preliminary analyses in mice revealed an unexpected high sensitivity of Bourbon virus to the antiviral effects of interferon. We therefore hypothesize that Bourbon virus lacks a virulence factor that normally controls the antiviral action of the interferon system. By directly comparing the interferon induction and pathogenic potential of Bourbon virus with other Thogotovirus isolates in cell culture and in the mouse model and by analysing recombinant viruses with defects in potential viral gene products, we plan to identify virulence factors including possible interferon-antagonists that account for the high virulence of Thogotoviruses. Finally, we plan to evaluate therapeutic options to respond to future zoonotic transmissions of Bourbon virus.

波旁病毒属于正粘病毒科内的索戈托病毒属。Thogotovirus从非洲，亚洲和南欧的蜱虫中分离出来，已知会在农场动物中引起严重疾病，但在人类中很少。因此，最近从美国一例患有严重发热性疾病并死于多器官衰竭的致命病例中分离出一种新的索戈托病毒，称为波旁病毒，这令人惊讶。导致这种严重疾病的结果的机制是未知的，但可能与一个意想不到的毒力的波旁病毒或缺陷的主机先天免疫response.To提供这些假说的证据，我们要研究的影响干扰素系统的致病潜力的波旁病毒在体外和在一个合适的小鼠模型。此外，我们希望确定分子决定因素解释这种新出现的Thogotovirus干扰素敏感性。与其他索戈托病毒相反，在小鼠中的初步分析显示，波旁病毒对干扰素的抗病毒作用具有意想不到的高敏感性。因此，我们假设波旁病毒缺乏一个毒力因子，通常控制干扰素系统的抗病毒作用。通过直接比较干扰素诱导和致病潜力的波本病毒与其他Thogotovirus分离株在细胞培养和小鼠模型中，并通过分析重组病毒与缺陷的潜在病毒基因产物，我们计划确定毒力因子，包括可能的干扰素拮抗剂，占高毒力的Thogotovirus。最后，我们计划评估治疗方案，以应对未来波旁病毒的人畜共患传播。