Development of a Well-Characterized Rhesus Macaque Model of Ebola Virus Disease for Support of Product Development.
Development of a Well-Characterized Rhesus Macaque Model of Ebola Virus Disease for Support of Product Development.
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DOI：
10.3390/microorganisms9030489
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发表时间：
2021-02-26
期刊：
影响因子：
4.5
通讯作者：
Carrion R Jr
中科院分区：
文献类型：
--
作者：
Alfson KJ;Goez-Gazi Y;Gazi M;Staples H;Mattix M;Ticer A;Klaffke B;Stanfield K;Escareno P;Keiser P;Griffiths A;Chou YL;Niemuth N;Meister GT;Cirimotich CM;Carrion R Jr
埃博拉病毒（EBOV）是一种负义RNA病毒，可感染人类和非人灵长类动物，造成严重的健康后果。制定对策需要彻底了解宿主和病原体之间的相互作用以及疾病的过程。本研究的目的是在一致致死的恒河猴模型中进一步表征EBOV疾病，以支持遵循严格质量标准的良好表征的模型的开发。将恒河猴肌内暴露于EBOV，并在预定时间点对一组实施安乐死以表征疾病进展。第二组未计划安乐死，以分析生存率、生理学变化、临床病理学、终末病理学和遥测动力学。在第3天，观察到散发性病毒血症，并在淋巴结中观察到病理学证据。到第5天，在所有暴露于EBOV的动物中检测到病毒血症，并且在肝、脾和胃肠道组织中注意到病理学证据。这些数据支持这样的观点，即恒河猴中的EBOV感染是在压缩的时间尺度下与人类中的感染相似的快速全身性疾病。在感染的最早阶段观察到与疾病进展相关的生物标志物，从而鉴定用于治疗研究的潜在“治疗药物”。
Ebola virus (EBOV) is a negative-sense RNA virus that can infect humans and nonhuman primates with severe health consequences. Development of countermeasures requires a thorough understanding of the interaction between host and pathogen, and the course of disease. The goal of this study was to further characterize EBOV disease in a uniformly lethal rhesus macaque model, in order to support development of a well-characterized model following rigorous quality standards. Rhesus macaques were intramuscularly exposed to EBOV and one group was euthanized at predetermined time points to characterize progression of disease. A second group was not scheduled for euthanasia in order to analyze survival, changes in physiology, clinical pathology, terminal pathology, and telemetry kinetics. On day 3, sporadic viremia was observed and pathological evidence was noted in lymph nodes. By day 5, viremia was detected in all EBOV exposed animals and pathological evidence was noted in the liver, spleen, and gastrointestinal tissues. These data support the notion that EBOV infection in rhesus macaques is a rapid systemic disease similar to infection in humans, under a compressed time scale. Biomarkers that correlated with disease progression at the earliest stages of infection were observed thereby identifying potential “trigger-to-treat” for use in therapeutic studies.
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影响因子：
7.5
作者：
BICK, RL;BAKER, WF
通讯作者：
BAKER, WF
巨麦卡筋膜内肌内暴露于低剂量的低通过或细胞培养的苏丹病毒或埃博拉病毒。
DOI：
10.3390/v10110642
发表时间：
2018-11-16
期刊：
Viruses
影响因子：
--
作者：
Alfson KJ;Avena LE;Beadles MW;Worwa G;Amen M;Patterson JL;Carrion R Jr;Griffiths A
通讯作者：
Griffiths A
影响因子：
6.4
作者：
Osterholm MT;Moore KA;Kelley NS;Brosseau LM;Wong G;Murphy FA;Peters CJ;LeDuc JW;Russell PK;Van Herp M;Kapetshi J;Muyembe JJ;Ilunga BK;Strong JE;Grolla A;Wolz A;Kargbo B;Kargbo DK;Sanders DA;Kobinger GP
通讯作者：
Kobinger GP
影响因子：
4.7
作者：
Alfson, Kendra J.;Avena, Laura E.;Griffiths, Anthony
通讯作者：
Griffiths, Anthony
影响因子：
6.4
作者：
McElroy, Anita K.;Erickson, Bobbie R.;Spiropoulou, Christina F.
通讯作者：
Spiropoulou, Christina F.