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

橄榄狒狒，研究寨卡病毒生物学和发病机制的转化模型

• 批准号: 9264356
• 负责人: James F Papin
• 金额: $ 22.2万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-01 至 2018-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9264356
• 关键词: Adult; Africa; Age; Americas; Antibody-Dependent Enhancement; Area; Asia; Biology; Bite; Blood; Blood specimen; Bordetella pertussis; Brazil; Breeding; CD8-Positive T-Lymphocytes; Cerebrospinal Fluid; Cessation of life; Clinical; Congenital Abnormality; Contracts; Culicidae; Dengue Infection; Dengue Virus; Development; Disease; Disease Outbreaks; Emergency Situation; Environmental Wind; Epidemic; Epitopes; Evaluation; Family; Female; Fetal Growth Retardation; Flavivirus; Foundations; French Polynesia; General Population; Gold; Guillain-Barré Syndrome; Human; Humoral Immunities; Immune response; Immunity; Immunoglobulin G; Immunoglobulin M; Infection; Inflammatory Response; International; Intervention; Investigation; Japanese encephalitis virus; Kinetics; Link; Measures; Microcephaly; Modeling; Morbidity - disease rate; Neural Tube Defects; Neurologic; Observational Study; Oklahoma; Papio; Papio anubis; Pathogenesis; Pathogenicity; Pathology; Placentation; Population; Pregnant Women; Prevention; RNA Viruses; Research; Resolution; Resources; Respiratory syncytial virus; Role; Saliva; Seminal fluid; Serotyping; Serum; Study models; Symptoms; Testing; Therapeutic; Tissues; Translations; Uganda; Urine; Vagina; Viral; Viremia; Virulence; Virus; Virus Diseases; West Nile virus; Work; World Health Organization; Yellow fever virus; Zika Virus; cytokine; experience; fetal; infectious disease model; male; maternal vaccination; member; mortality; nervous system disorder; neutralizing antibody; novel therapeutics; novel vaccines; pathogen; pregnant; prevent; public health emergency; response; secondary infection; therapeutic development; tool; vaccine candidate; vaccine development; vaccine evaluation

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.

抽象的 Zika病毒（ZIKV）是Flaviviridae家族的单链RNA病毒。与其他更善良的密切相关 Flavivrus家族的知名成员，包括黄热病病毒，西尼罗河病毒（WNV），日语 脑炎病毒和登革热病毒（DENV），通过被感染的蚊子的咬伤传播。 目前，美洲正在从这种新兴病毒中爆发世界健康 由于新发现的协会 严重胎儿异常的ZIKV感染，包括神经管缺陷和宫内生长限制。 以前，ZIKV仅与非洲和亚洲的轻度疾病有关，自从它是地方性的 1947年在乌干达的发现以及与ZIKV感染相关的发病率的增加不好 理解。在法属波利尼西亚和巴西以及 由于抗体依赖性增强的范式，被假设为促成因子 严重DENV感染中的疾病（ADE），但ZIKV疾病中发生ADE的证据尚未 经过证明。 阐明负责增加ZIKV毒力的机制以及 疫苗和治疗剂至关重要。但是，目前尚无既定的翻译模型 研究ZIKV病理生物学。橄榄狒狒帕皮奥·阿努比斯（Papio Anubis）已成为翻译 多种病原体（例如Bordetella buttussis和呼吸综合病毒）的传染病模型 以及包括WNV和DENV在内的其他黄病毒。我们建议为目的进行研究 将狒狒建立为ZIKV疾病的转化模型，并假设以前 DENV感染将影响模型中对ZIKV的致病性和免疫反应。 拟议的研究将共同​​建立ZIKV疾病的翻译模型，并开始澄清 发病率增加的机制。