Laboratory of Experimental Virology, Department of Medical Microbiology and Infection Prevention, Amsterdam institute for Infection & Immunity, Amsterdam UMC, University of Amsterdam, the Netherlands.
Global Child Health Group, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, the Netherlands.
PLoS Negl Trop Dis. 2020 Oct 28;14(10):e0008856. doi: 10.1371/journal.pntd.0008856. eCollection 2020 Oct.
The Orthobunyavirus genus comprises a wide range of arthropod-borne viruses which are prevalent worldwide and commonly associated with central nervous system (CNS) disease in humans and other vertebrates. Several orthobunyaviruses have recently emerged and increasingly more will likely do so in the future. Despite this large number, an overview of these viruses is currently lacking, making it challenging to determine importance from a One Health perspective. Causality is a key feature of determining importance, yet classical tools are unfit to evaluate the causality of orthobunyaviral CNS disease. Therefore, we aimed to provide an overview of orthobunyaviral CNS disease in vertebrates and objectify the causality strength of each virus. In total, we identified 27 orthobunyaviruses described in literature to be associated with CNS disease. Ten were associated with disease in multiple host species of which seven included humans. Seven viruses were associated with both congenital and postnatal CNS disease. CNS disease-associated orthobunyaviruses were spread across all known Orthobunyavirus serogroups by phylogenetic analyses. Taken together, these results indicate that orthobunyaviruses may have a common tendency to infect the CNS of vertebrates. Next, we developed six tailor-made causality indicators and evaluated the causality strength of each of the identified orthobunyaviruses. Nine viruses had a 'strong' causality score and were deemed causal. Eight had a 'moderate' and ten a 'weak' causality score. Notably, there was a lack of case-control studies, which was only available for one virus. We, therefore, stress the importance of proper case-control studies as a fundamental aspect of proving causality. This comprehensible overview can be used to identify orthobunyaviruses which may be considered causal, reveal research gaps for viruses with moderate to low causality scores, and provide a framework to evaluate the causality of orthobunyaviruses that may newly emerge in the future.
布尼亚病毒科包含广泛的节肢动物传播病毒，这些病毒在全球范围内普遍存在，通常与人类和其他脊椎动物的中枢神经系统 (CNS) 疾病有关。最近有几种布尼亚病毒出现，未来可能会出现更多的病毒。尽管数量众多，但目前缺乏对这些病毒的概述，因此从“One Health”的角度很难确定其重要性。因果关系是确定重要性的关键特征，但经典工具不适合评估布尼亚病毒 CNS 疾病的因果关系。因此，我们旨在提供脊椎动物布尼亚病毒 CNS 疾病的概述，并客观评估每种病毒的因果关系强度。总共，我们在文献中确定了 27 种与 CNS 疾病相关的布尼亚病毒。其中 10 种与多种宿主物种的疾病有关，其中 7 种包括人类。有 7 种病毒与先天性和后天性 CNS 疾病有关。通过系统发育分析，与 CNS 疾病相关的布尼亚病毒分布在所有已知的布尼亚病毒血清群中。总的来说，这些结果表明布尼亚病毒可能有一种共同的倾向，即感染脊椎动物的中枢神经系统。接下来，我们开发了六个定制的因果关系指标，并评估了每个已确定的布尼亚病毒的因果关系强度。9 种病毒的因果关系评分较高，被认为是因果关系。8 种病毒的因果关系评分为中度，10 种病毒的因果关系评分为弱。值得注意的是，缺乏病例对照研究，而这种研究仅适用于一种病毒。因此，我们强调适当的病例对照研究作为证明因果关系的基本方面的重要性。这个易于理解的概述可以用于识别可能被认为是因果关系的布尼亚病毒，揭示因果关系评分中等至较低的病毒的研究差距，并提供一个框架来评估未来可能新出现的布尼亚病毒的因果关系。
