The Olive Baboon, a translational model for the study of Zika virus biology and pathogenesis

摘要 寨卡病毒（ZIKV）是黄病毒科的单链RNA病毒。与其他更密切相关- 黄病毒家族的已知成员包括黄热病毒、西尼罗河病毒（WNV）、日本病毒、 ZIKV是一种病毒，与登革热病毒（DENV）一样，ZIKV通过被感染的蚊子叮咬传播。 目前，美洲正在经历这种新出现的病毒的爆发， 该组织已宣布国际关注的公共紧急状态，由于新成立的协会， ZIKV感染伴严重胎儿畸形，包括神经管缺陷和宫内生长受限。 以前，ZIKV仅与非洲和亚洲的轻度疾病有关，自2010年以来， 1947年在乌干达发现ZIKV，目前与ZIKV感染相关的发病率增加， 明白法属波利尼西亚和巴西分别同时爆发和逐渐减弱的DENV疫情， 由于公认的抗体依赖性增强模式， 严重DENV感染中的疾病（ADE），但ZIKV疾病中发生ADE的证据尚未得到证实。 证明了 阐明负责ZIKV的毒力增加以及ZIKV的发展的机制。 疫苗和治疗方法至关重要。然而，目前还没有建立翻译模型， 研究ZIKV的病理学橄榄狒狒，Papio anubis，被认为是一种 百日咳杆菌和呼吸道合胞病毒等多种病原体的传染病模型 以及包括WNV和DENV的其它黄病毒。我们建议进行研究，目的是 建立狒狒作为ZIKV疾病的转化模型，并假设先前的 感染DENV将影响模型内对ZIKV的致病性和免疫应答。 所提出的研究将共同建立ZIKV疾病的转化模型，并开始阐明ZIKV疾病的基因表达。 发病率上升的机制。

Abstract Zika virus (ZIKV) is single stranded RNA virus of the Flaviviridae family. Closely related to other more well- known members of the flavivrus family including Yellow Fever virus, West Nile virus (WNV), Japanese Encephalitis virus, and Dengue virus (DENV), ZIKV is transmitted through the bite of an infected mosquito. Currently the Americas are experiencing an outbreak from this emerging virus that the World Health Organization has declared a Public Emergency of International Concern due to the newly found association of ZIKV infection with severe fetal anomalies including neural tube defects and intrauterine growth restriction. Previously ZIKV was only associated with mild disease in Africa and Asia where it has been endemic since its discovery in Uganda in 1947 and the current increase in morbidity associated with ZIKV infection is not well understood. Concurrent and waning DENV outbreaks, in French Polynesia and Brazil and respectively, have been hypothesized as a contributing factor due to the accepted paradigm of antibody-dependent enhancement of disease (ADE) in severe DENV infection, but evidence of ADE occurring in ZIKV disease has not been proven. Elucidation of the mechanisms responsible for the increased virulence of ZIKV as well as the development of vaccines and therapeutics are paramount. However, currently there are no established translational models in which to study ZIKV pathobiology. The olive baboon, Papio anubis, has been advanced as a translational model of infectious disease for multiple pathogens such as Bordetella pertussis and Respiratory Syncytial virus as well as other flaviviruses including WNV and DENV. We propose to conduct studies for the purpose of establishing the baboon as a translational model of ZIKV disease, and hypothesize that previous infection with DENV will impact the pathogenicity and immune response to ZIKV within the model. Together the proposed studies will establish a translational model of ZIKV disease and begin to clarify the mechanism of increased morbidity.