Bluetongue virus changes the emission of volatile organic chemicals in the body odour of sheep and cattle during infection

蓝舌病毒感染期间改变羊和牛体味中挥发性有机化学物质的排放

• 批准号: BB/T014601/1
• 负责人: Christopher Sanders
• 金额: $ 60.07万
• 依托单位: The Pirbright Institute
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FT014601%2F1
• 关键词: Bluetongue; virus; changes; emission; volatile

Mammals, including humans, constantly emit hundreds of volatile organic chemicals (VOCs) as part of body odour and their individual composition alters in response to underlying biological and environmental influences. These chemicals will also change in response to diseases and infections. Innovative new technologies are being used to explore odour-based biomarkers in breath, skin emissions and excretions as diagnostics tools for the early detection of difficult-to-diagnose conditions like cancer and tuberculosis. The emission of VOCs is of particular importance for vector-borne pathogens such as the malaria parasite or arthropod-borne viruses (arboviruses) such as Zika virus, as insects who transmit these pathogens use specific chemicals in body odour (semiochemicals) as one way of finding their host. An emerging field of research is investigating how vector-borne pathogens modify the body odour of infected hosts to identify if infection-induced changes to body odour semiochemicals subsequently alter the attraction of insect vectors. Studies based on human: mosquito: malaria interactions are at the forefront of this research and recent high-profile outcomes have reported that mosquitoes are more attracted to infected individuals. Most intriguingly vector mosquitoes might be specifically attracted to those infection stages of the parasite that will enhance successful transmission. Despite the overall importance surprising little is known in regards to the effect of arbovirus infections on body odour modification and subsequent insect vector attraction. Most arbovirus infections of humans and animals are acute and characterised by shorter periods of virus presence in the blood (viraemia), making the collection of body odour emissions during natural infections across rapidly changing stages of infection challenging. In contrast, while the development of mouse models of infection offers flexibility and a vast associated array of interrogative tools, they are limited in their relevance to natural infections. Arboviruses cause highly important diseases also in livestock. Culicoides-borne viruses such as bluetongue virus (BTV) can cause devastating disease in some species of ruminants and are a current major threat to the UK agriculture sector due to ongoing outbreaks in continental Europe. Combining the unique expertise of all project partners we have created a novel and flexible infection system that remains relevant to the real world and translatable to field application. In a proof-of-concept study we will investigate the hypothesis that BTV infection changes VOC profiles in the body odour of the main natural hosts, cattle and sheep. Detected BTV-induced host odour changes can subsequently be assessed for their potential to modify the attraction of insect vectors as well as highlight opportunities for novel diagnostic tools. BTV causes more severe disease in sheep than in cattle despite an equally high level of virus in the blood. Therefore this study system will also determine if odour based diagnostic technology can be developed to detect viral infections even in the absence of clinical signs. The latter is of vital importance as odour-based detection of non-diseased but infected individuals could transform both pen-side diagnostic systems and control measures such as repellent and attractant chemicals available for insect vector control. Study outcomes will immediately improve our understanding of BTV transmission and highlight opportunities for targeted control of Culicoides vectors. Importantly study results can in the future be transferred to other highly important viral pathogens of livestock and identify if different virus species induce specific odour changes. Demonstrating this will be of vital interest not only for other vector-borne viral diseases including those of humans, but also significantly advance the emerging field of odour-based detection of viral infections.

哺乳动物，包括人类，不断释放数百种挥发性有机化学物质（VOCs），作为体味的一部分，它们的个体成分会随着潜在的生物和环境影响而改变。这些化学物质也会因疾病和感染而发生变化。创新的新技术正被用于探索呼吸、皮肤排放物和排泄物中基于气味的生物标志物，作为早期发现癌症和结核病等难以诊断的疾病的诊断工具。挥发性有机化合物的排放对于疟疾寄生虫等媒介传播的病原体或寨卡病毒等节肢动物传播的病毒（虫媒病毒）尤为重要，因为传播这些病原体的昆虫利用体味中的特定化学物质（半化学物质）作为寻找宿主的一种方式。一个新兴的研究领域是调查媒介传播的病原体如何改变受感染宿主的体味，以确定感染引起的体味半化学物质的变化是否随后改变了昆虫媒介的吸引力。基于人类：蚊子：疟疾相互作用的研究处于这项研究的前沿，最近的引人注目的结果报告说，蚊子更容易被感染的个体吸引。最有趣的是，媒介蚊子可能会特别被寄生虫的感染阶段所吸引，这将增强成功传播。尽管总体重要性令人惊讶，但关于虫媒病毒感染对体臭修饰和随后的昆虫媒介吸引的影响，我们知之甚少。人类和动物的大多数虫媒病毒感染是急性的，其特点是病毒在血液中存在的时间较短（病毒血症），这使得在快速变化的感染阶段自然感染期间收集体臭散发物具有挑战性。相比之下，虽然小鼠感染模型的发展提供了灵活性和大量相关的疑问工具，但它们在与自然感染的相关性方面受到限制。虫媒病毒也在牲畜中引起非常重要的疾病。库蠓传播的病毒，如蓝舌病病毒（BTV），可在某些反刍动物物种中引起毁灭性疾病，由于欧洲大陆持续爆发，目前是英国农业部门的主要威胁。结合所有项目合作伙伴的独特专业知识，我们创造了一种新颖灵活的感染系统，与现实世界保持相关，并可转化为现场应用。在一项概念验证研究中，我们将调查BTV感染改变主要天然宿主牛和羊体味中VOC谱的假设。检测到的btv诱导的宿主气味变化随后可以评估其改变昆虫媒介吸引力的潜力，并突出新的诊断工具的机会。尽管血液中的病毒水平同样高，但BTV在绵羊中引起的疾病比在牛中更严重。因此，该研究系统还将确定是否可以开发基于气味的诊断技术来检测病毒感染，即使没有临床症状。后者是至关重要的，因为基于气味的检测非患病但感染的个体可以改变围栏侧诊断系统和控制措施，例如用于昆虫媒介控制的驱避和引诱化学品。研究结果将立即提高我们对BTV传播的理解，并为有针对性地控制库蠓媒介提供机会。重要的是，研究结果可以在未来转移到其他非常重要的家畜病毒病原体，并确定不同的病毒种类是否会引起特定的气味变化。证明这一点不仅对包括人类在内的其他媒介传播的病毒性疾病至关重要，而且还将大大推进基于气味的病毒感染检测这一新兴领域。