University of Washington Arboviral Research Network (UWARN)

摘要：联合世界抗病毒研究网络（UWARN，以前称为华盛顿大学虫媒病毒研究网络）将通过对包括登革热、基孔肯雅病毒和寨卡病毒等当前高负担病原体在内的虫媒病毒进行研究，应对新发和再发传染病。虫媒病毒还包括新出现和再出现的病毒，如马亚罗病毒、乌纳病毒、乌苏图病毒、日本脑炎病毒、黄热病病毒、克里米亚-刚果出血热病毒和Oropouche病毒。UWARN将利用西澳大学大流行疾病防范联盟（原metcenter）和巴西、塞内加尔、南非、巴基斯坦和台湾的强大研究实验室合作伙伴，以及西澳大学全球卫生部在能力建设方面的全球影响力。世卫组织的国际合作伙伴拥有以机构为基础和以人群为基础的队列，以开展计划中的研究和监测新病毒的出现。拟议的UWARN研究将创造新的人类病毒中和单克隆抗体（hu - nmab），可用于治疗或诊断。UWARN的研究还将创造新的诊断方法，由蛋白质设计研究所（Institute for Protein Design）从头开始创造，即当体液中存在病毒抗体时释放光的人造蛋白质。最后，UWARN研究将产生对病毒如何操纵人类先天免疫系统的理解，这些信息将用于设计生物标志物来预测严重疾病，以及建议在虫媒病毒感染后可能导致更好结果的宿主定向治疗。拟议的技术是通用的，可以迅速适应任何未来出现的虫媒病毒威胁。UWARN的合作伙伴涵盖病毒学、细菌学、真菌学和寄生虫感染，因此UWARN可以应对各种新出现的传染病威胁。UWARN国际实验室拥有先进的能力，包括生物储存库与发电机电源备用-80℃冰柜，下一代测序（NGS）能力，荧光细胞分选和BSL-3密封设施。UWARN队列从患有已知和未知虫媒病毒性疾病的急性发热性疾病的个体中采集了生物库样本，伙伴关系站点已准备好进行基于人群和设施的前瞻性样本收集。UWARN实验室将使用宏基因组NGS检测附属队列中出现的新型病毒。UWARN合作伙伴已与昆虫学家和兽医合作，根据需要对节肢动物媒介和动物宿主进行取样。其他创新能力包括巴西UWARN合作伙伴的移动面包车，其车载NGS功能可在18小时内实现实时、现场病毒测序和采样，并进行病毒鉴定。第二个合作伙伴，塞内加尔的IRESSEF，计划在塞内加尔建立一个类似的病毒采样和测序移动工具，巴西的小组将在技术转让和最佳实践方面与IRESSEF合作。UWARN合作伙伴将作为其他新兴传染病研究中心（EIDRC）的资源，提供单克隆抗体、蛋白质设计和宿主定向治疗方面的专业知识。

Abstract: The United World Antiviral Research Network (UWARN, formerly referred to as the University of Washington Arboviral Research Network) will address emerging and re-emerging infectious diseases by carrying out research on arboviruses that include current high burden pathogens including dengue, chikungunya, and Zika viruses. Arboviruses also include emerging and re-emerging viruses such as Mayaro, Una, Usutu, Japanese encephalitis, yellow fever, Crimean-Congo hemorrhagic fever, and Oropouche viruses. UWARN will leverage the UW Alliance (formerly Metacenter) for Pandemic Disease Preparedness and strong research laboratory partners in Brazil, Senegal, South Africa, Pakistan and Taiwan as well as the UW Department of Global Health global reach in capacity building. The UWARN international Collaborating Partners have institution-based and population-based cohorts in place to carry out the planned research and monitor for new virus emergence. The proposed UWARN research will create new human viral-neutralizing monoclonal antibodies (Hu-nMabs) that can be used as therapeutics or diagnostics. UWARN research will also create new diagnostics, created ab initio by the Institute for Protein Design, as artificial proteins that release light when antibodies to virus are present in body fluids. Finally, UWARN research will generate an understanding of how viruses manipulate the human innate immune system, and this information will be used to design biomarkers to predict severe disease as well as to suggest host-directed therapies that could lead to better outcomes after arboviral infection. The proposed technologies are generic and could be rapidly adapted to any future emerging arbovirus threat. UWARN collaborators span virology, bacteriology, mycology, and parasitic infections, such that UWARN can respond to diverse emerging infectious diseases threats. UWARN international laboratories have advanced capabilities including biorepositories with generator-power backed-up -80C freezers, next-generation sequencing (NGS) capabilities, fluorescence cell sorting, and BSL-3 containment facilities. UWARN cohorts have biobanked samples taken from individuals during acute febrile illnesses, with known and unknown arboviral diseases, and partnership sites are poised for prospective collection of population and facility–based samples. UWARN labs will use metagenomic NGS to detect novel viral emergence in affiliated cohorts. UWARN Partners have collaborating entomologists and veterinarians to sample arthropod vectors and animal reservoirs as needed. Additional innovative capacity included the Brazil UWARN partner’s mobile van with on board NGS capability for real-time, on-site viral sequencing and sampling to viral identification in less than 18 hrs. A second partner, IRESSEF in Senegal, plans to set up a similar mobile vehicle for viral sampling and sequencing in Senegal and the Brazil group will collaborate with IRESSEF on technology transfer and best practices. UWARN partners will serve as a resource to other Emerging Infectious Diseases Research Centers (EIDRC) providing expertise in monoclonal antibodies, protein design, and host directed therapies.