Institute of Virology, Medical Center-University of Freiburg, Freiburg, Germany.
Faculty of Mathematics and Computer Science, Friedrich Schiller University, Jena, Germany.
J Virol. 2022 Mar 9;96(5):e0155621. doi: 10.1128/JVI.01556-21. Epub 2022 Jan 12.
Thogotoviruses are tick-borne arboviruses that comprise a unique genus within the family. Infections with thogotoviruses primarily cause disease in livestock with occasional reports of human infections suggesting a zoonotic potential. In the past, multiple genetically distinct thogotoviruses were isolated mostly from collected ticks. However, many aspects regarding their phylogenetic relationships, morphological characteristics, and virulence in mammals remain unclear. For the present comparative study, we used a collection of 10 different thogotovirus isolates from different geographic areas. Next-generation sequencing and subsequent phylogenetic analyses revealed a distinct separation of these viruses into two major clades, the Thogoto-like and Dhori-like viruses. Electron microscopy demonstrated a heterogeneous morphology with spherical and filamentous particles being present in virus preparations. To study their pathogenicity, we analyzed the viruses in a small animal model system. In intraperitoneally infected C57BL/6 mice, all isolates showed a tropism for liver, lung, and spleen. Importantly, we did not observe horizontal transmission to uninfected, highly susceptible contact mice. The isolates enormously differed in their capacity to induce disease, ranging from subclinical to fatal outcomes. multistep passaging experiments of two low-pathogenic isolates showed no increased virulence and sequence analyses of the passaged viruses indicated a high stability of the viral genomes after 10 mouse passages. In summary, our analysis demonstrates the broad genetic and phenotypic variability within the thogotovirus genus. Moreover, thogotoviruses are well adapted to mammals but their horizontal transmission seems to depend on ticks as their vectors. Since their discovery over 60 years ago, 15 genetically distinct members of the thogotovirus genus have been isolated. These arboviruses belong to the Orthomyxovirus family and share many features with influenza viruses. However, numerous of these isolates have not been characterized in depth. In the present study, we comparatively analyzed a collection of 10 different thogotovirus isolates to answer basic questions about their phylogenetic relationships, morphology, and pathogenicity in mice. Our results highlight shared and unique characteristics of this diverse genus. Taken together, these observations provide a framework for the phylogenic classification and phenotypic characterization of newly identified thogotovirus isolates that could potentially cause severe human infections as exemplified by the recently reported, fatal Bourbon virus cases in the United States.
坨型病毒属于蜱传黄病毒科，是一个独特的属。坨型病毒感染主要引起家畜疾病，偶尔有人类感染的报告，表明其具有人畜共患的潜力。过去，多种遗传上不同的坨型病毒主要从采集的蜱中分离出来。然而，它们在哺乳动物中的系统发育关系、形态特征和毒力等许多方面仍不清楚。在目前的比较研究中，我们使用了来自不同地理区域的 10 种不同坨型病毒分离株的集合。下一代测序和随后的系统发育分析表明，这些病毒明显分为两个主要分支，即 Thogoto 样病毒和 Dhori 样病毒。电子显微镜显示，病毒制剂中存在球形和丝状颗粒，具有异质形态。为了研究它们的致病性，我们在小动物模型系统中分析了这些病毒。在经腹腔感染 C57BL/6 小鼠中，所有分离株均表现出对肝脏、肺和脾脏的嗜性。重要的是，我们没有观察到对未感染的高度易感接触小鼠的水平传播。这些分离株在诱导疾病的能力上有很大的差异，从亚临床到致命的结果不等。对两种低致病性分离株的多步传代实验表明，病毒毒力没有增加，传代病毒的序列分析表明，病毒基因组在经过 10 次小鼠传代后高度稳定。总之，我们的分析表明坨型病毒属内存在广泛的遗传和表型变异性。此外，坨型病毒很好地适应了哺乳动物，但它们的水平传播似乎依赖于作为其媒介的蜱。自 60 多年前发现以来，已分离出坨型病毒属的 15 个具有遗传差异的成员。这些虫媒病毒属于正粘病毒科，与流感病毒有许多共同特征。然而，许多这些分离株尚未得到深入的描述。在本研究中，我们比较分析了一组 10 种不同的坨型病毒分离株，以回答关于它们的系统发育关系、形态和在小鼠中的致病性的基本问题。我们的结果突出了这个多样化属的共同和独特特征。总之，这些观察结果为新鉴定的坨型病毒分离株的系统发育分类和表型特征提供了一个框架，这些分离株可能会导致严重的人类感染，如最近在美国报告的致命 Bourbon 病毒病例所证明的那样。
