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

哺乳动物，包括人类，不断释放数百种挥发性有机化合物(VOC)作为体味的一部分，它们的个体组成会因潜在的生物和环境影响而改变。这些化学物质也会因应疾病和感染而发生变化。创新的新技术正被用于探索呼吸、皮肤排放和排泄物中基于气味的生物标记物，作为诊断工具，用于早期检测癌症和结核病等难以诊断的疾病。VOCs的排放对于媒介传播的病原体，如疟疾寄生虫或节肢动物传播的病毒(虫媒病毒)，如寨卡病毒，具有特别重要的意义，因为传播这些病原体的昆虫使用体味中的特定化学物质(信号化学物质)作为寻找宿主的一种方式。一个新兴的研究领域正在研究媒介传播的病原体如何改变受感染宿主的体味，以确定感染诱导的体味信号化学物质是否会随后改变昆虫媒介的吸引力。基于人、蚊子和疟疾相互作用的研究是这项研究的前沿，最近备受瞩目的结果报告说，蚊子更容易被感染的人吸引。最耐人寻味的是，媒介蚊子可能特别被寄生虫的感染阶段吸引，这将加强成功的传播。尽管虫媒病毒感染对体味改变和随后的昆虫媒介吸引的影响，令人惊讶的是，关于虫媒病毒感染对体味修改和随后的昆虫媒介吸引的影响，令人惊讶的是知之甚少。大多数人和动物的虫媒病毒感染都是急性的，其特点是病毒在血液中的存在时间较短(病毒血症)，这使得在快速变化的感染阶段收集自然感染期间的体味排放具有挑战性。相比之下，尽管小鼠感染模型的发展提供了灵活性和大量相关的质疑工具，但它们与自然感染的相关性有限。虫媒病毒也会在家畜中引起高度重要的疾病。库蚊传播的病毒，如蓝舌病毒(BTV)，可在某些种类的反刍动物中引起毁灭性疾病，由于欧洲大陆持续爆发，目前是对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，我们创建了一种新颖而灵活的感染系统，该系统仍然与现实世界相关，并可翻译为现场应用。在一项概念验证研究中，我们将调查BTV感染改变主要自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它们改变昆虫媒介的吸引力的潜力，以及突出新诊断工具的机会。BTV对绵羊造成的疾病比对牛更严重，尽管血液中的病毒水平同样高。因此，这项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，即使在没有临床症状的情况下也是如此。后者是至关重要的，因为对未患病但受感染的个体进行基于气味的检测可以改变围栏边的诊断系统和控制措施，如可用于昆虫媒介控制的驱避剂和引诱剂。研究结果将立即提高我们对BTV传播的了解，并突出有针对性地控制库蚊病媒的机会。重要的是，未来可以将研究结果转移到家畜的其他高度重要的病毒病原体上，并确定不同的病毒种类是否会导致特定的气味变化。证明这一点不仅对包括人类在内的其他媒介传播的病毒疾病具有重要意义，而且还将显著推动基于气味的病毒感染检测这一新兴领域的发展。

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.