COVID 19: LESSONS FROM FATAL CORONAVIRUS INFECTIONS IN COMPANION ANIMALS

COVID 19：伴侣动物致命冠状病毒感染的教训

• 批准号: BB/V011308/1
• 负责人: Lucy Jane Davison
• 金额: $ 25.59万
• 依托单位: Royal Veterinary College
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FV011308%2F1
• 关键词: COVID; 19; LESSONS; FATAL; CORONAVIRUS

Companion animals are susceptible to coronaviruses, including SARS-CoV-2. This proposal addresses 3 important unmet needs:1: We do not know precisely why certain individuals or ethnic groups are more susceptible to COVID-19, and whether this difference in susceptiblity has a genetic basis.2: SARS-Cov2 is a novel virus, so we are poorly prepared to recognise or manage unforeseen chronic or late-presenting medical complications of COVID-19.3: Dogs and cats may act as a reservoir for future zoonotic coronaviruses, but the responses of these species to coronaviruses are poorly understood.We hypothesise that transcriptomic and whole genome sequencing analysis in extreme responses to veterinary coronaviruses will reveal reveal new genetic susceptibilty loci and treatment targets relevant to COVID-19. These data will also increase preparedness for delayed COVID-19 complications and novel future zoonotic coronaviruses.CANINE RESPIRATORY CORONAVIRUS (CRCoV) is a highly contagious respiratory beta-coronavirus sharing many parallels with SARS-CoV-2. Almost 100% of dogs sero-convert within 21 days of exposure in affected kennels. Many dogs are asymptomatic, some develop 'kennel cough' and a small number are euthanased with severe bronchopneumonia. CRCoV represents a spontaneous beta-coronavirus model which shares many parallels with SARS-CoV-2 and can improve our understanding of genetic risk factors associated with mild and severe coronavirus infections. FELINE INFECTIOUS PERITONITIS (FIP) is a fatal multi-systemic inflammatory disease, occurring months to years after coronavirus infection. FIP shares features with COVID-19 associated Kawasaki-like syndrome in children. FIP is caused by a rare, in-host, mutation of a common feline enteric alpha-coronavirus, changing its tropism from epithelial cells to macrophages. Notably, the SARS-CoV-1 S gene is a mosaic containing FIP-derived sequence. FIP offers an excellent model to examine serious long-term consequences of coronavirus infectionRESEARCH PROPOSAL: Utilising unique veterinary tissue archives from dogs and cats with spontanous coronavirus infections, we will use Whole Genome Sequencing (WGS) and RNA-Sequencing (RNA-Seq) to identify host genetic factors and transcriptomic events associated with severe complications of veterinary coronaviruses in dogs and cats. TRANSLATIONAL POTENTIAL: This is a collaborative 'One Health' proposal at the interface of veterinary and human medicine, so we are ideally poised to translate findings promptly.

伴侣动物易感染冠状病毒，包括SARS-CoV-2。该提案解决了3个重要的未满足的需求：1：我们不确切知道为什么某些个人或种族群体更容易感染COVID-19，以及这种易感性的差异是否具有遗传基础。2：SARS-Cov 2是一种新型病毒，因此我们对识别或管理不可预见的COVID-19慢性或晚期医学并发症的准备不足。3：狗和猫可能是未来人畜共患冠状病毒的储存库，但这些物种对冠状病毒的反应知之甚少。我们假设，对兽医冠状病毒极端反应的转录组和全基因组测序分析将揭示与COVID-19相关的新的遗传易感性位点和治疗靶点。这些数据还将提高对延迟的COVID-19并发症和未来新型人畜共患冠状病毒的准备。犬冠状病毒（CRCoV）是一种高度传染性的呼吸道β-冠状病毒，与SARS-CoV-2有许多相似之处。在受影响的犬舍中，几乎100%的犬在暴露后21天内发生血清转化。许多狗是无症状的，一些发展“犬舍咳嗽”和少数被安乐死与严重的支气管扩张症。CRCoV代表了一种自发的β-冠状病毒模型，它与SARS-CoV-2有许多相似之处，可以提高我们对与轻度和重度冠状病毒感染相关的遗传风险因素的理解。猫感染性腹膜炎（FIP）是一种致命的多系统炎症性疾病，发生在冠状病毒感染后数月至数年。FIP与COVID-19相关的儿童川崎病样综合征具有相同的特征。FIP是由一种常见的猫肠道α-冠状病毒的罕见的宿主内突变引起的，其嗜性从上皮细胞变为巨噬细胞。值得注意的是，SARS-CoV-1 S基因是含有FIP衍生序列的嵌合体。FIP提供了一个很好的模型来检查冠状病毒感染的严重长期后果研究建议：利用来自自发性冠状病毒感染的狗和猫的独特兽医组织档案，我们将使用全基因组测序（WGS）和RNA测序（RNA-Seq）来识别与犬和猫中兽医冠状病毒严重并发症相关的宿主遗传因素和转录组事件。翻译潜力：这是一个在兽医和人类医学界面上的合作“一个健康”提案，因此我们非常愿意迅速翻译研究结果。