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.

摘要 寨卡病毒(Zika Virus，ZIKV)是黄病毒科单链RNA病毒。与其他井密切相关- 黄病毒属的已知成员包括黄热病病毒、西尼罗河病毒、日本 脑炎病毒和登革病毒(DENV)，ZIKV通过受感染蚊子的叮咬传播。 目前美洲正在经历一场由这种新出现的病毒爆发的疫情，世界卫生组织 组织已宣布进入国际关注的公共紧急状态，因为新发现的 ZIKV感染伴有严重的胎儿畸形，包括神经管缺陷和胎儿宫内生长受限。 此前，寨卡病毒只与非洲和亚洲的轻微疾病有关，自其流行以来，它一直在那里流行 1947年在乌干达发现，目前与寨卡病毒感染相关的发病率增加不是很好 明白了。分别在法属波利尼西亚和巴西同时爆发和减弱的DENV疫情 由于公认的抗体依赖增强的范例，被假设为一个促成因素 在严重的DENV感染中出现ADE，但在ZIKV病中发生ADE的证据尚未得到证实 已经证明了。 ZIKV毒力增加的机制以及ZIKV的发展 疫苗和疗法是最重要的。但是，目前还没有确定的翻译模型 用来研究寨卡病毒的病理生物学。橄榄狒狒帕皮奥·阿努比斯已经被提升为翻译 百日咳杆菌、呼吸道合胞病毒等多病原传染病模型 以及其他黄病毒，包括西尼罗河病毒和登革热病毒。我们建议进行研究，目的是 将狒狒建立为寨卡病毒病的翻译模型，并假设以前 在模型中，DENV感染会影响ZIKV的致病性和免疫应答。 总之，拟议的研究将建立ZIKV疾病的翻译模型，并开始澄清 发病率增加的机制。