HUMAN TONSIL EXPLANTS AS A NOVEL MODEL FOR STUDYING DENGUE VIRUS INFECTION

 描述(申请人提供)：登革病毒(DENV)是最流行的蚊媒病毒，在人类中引起疾病，估计有25亿人面临感染DENV的风险，导致全球每年约3.9亿人感染。目前没有获得许可的疫苗或特定疗法，如果没有适当的支持治疗，严重登革热的死亡率可能超过20%。目前尚无具有免疫功能的登革热动物模型，这使得对登革热免疫发病机制的研究非常具有挑战性。这项应用的总体目标是开发一种新的体外人类扁桃体组织培养系统，以在整个淋巴组织细胞结构的背景下研究DENV感染。在初步研究中，我们已经证明，人类扁桃体组织培养支持WT DENV-2的生产性感染。通过优化这一组织培养系统，我们将努力实现我们的长期目标，即在人类扁桃体组织培养中表征所有四种血清型DENV的感染，其中我们可以在比现有基于细胞的系统更生理学的背景下研究DENV的细胞嗜性、感染动力学和免疫反应。

 DESCRIPTION (provided by applicant): Dengue virus (DENV) is the most prevalent mosquito-borne virus causing disease in humans, with an estimated 2.5 billion people at risk of DENV infection, resulting in about 390 million annual infections worldwide. There are currently no licensed vaccines or specific therapeutics, and the death rate for severe dengue without proper supportive care can be over 20%. There are no immune competent animal models for dengue disease, which has made immune pathogenesis studies very challenging. The overall objective of this application is to develop a novel ex vivo human tonsil histoculture system to study DENV infection in the context of whole lymphoid tissue cytoarchitecture. In preliminary studies, we have demonstrated that human tonsil histocultures support a productive infection of WT DENV-2. By optimizing this histoculture system, we will work toward achieving our long-term goal of characterizing the infection of the all four serotypes of DENV in human tonsil histocultures, in which we can study the cell tropism, infection kinetics and immune responses of DENV in a more physiological context than existing cell-based systems.