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开发一种特征明确的埃博拉病毒病恒河猴模型以支持产品研发。

Development of a Well-Characterized Rhesus Macaque Model of Ebola Virus Disease for Support of Product Development.

作者信息

Alfson Kendra J, Goez-Gazi Yenny, Gazi Michal, Staples Hilary, Mattix Marc, Ticer Anysha, Klaffke Benjamin, Stanfield Kaylee, Escareno Priscilla, Keiser Patrick, Griffiths Anthony, Chou Ying-Liang, Niemuth Nancy, Meister Gabe T, Cirimotich Chris M, Carrion Ricardo

机构信息

Disease Intervention and Prevention Program, Texas Biomedical Research Institute, 8715 W. Military Dr., San Antonio, TX 78227, USA.

Nonclinical Pathology Services, LLC, 3000 Stonebrooke Ln, Medina, OH 44256, USA.

出版信息

Microorganisms. 2021 Feb 26;9(3):489. doi: 10.3390/microorganisms9030489.

DOI:10.3390/microorganisms9030489
PMID:33652589
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7996724/
Abstract

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.

摘要

埃博拉病毒（EBOV）是一种负链RNA病毒，可感染人类和非人类灵长类动物，导致严重的健康后果。开发应对措施需要深入了解宿主与病原体之间的相互作用以及疾病进程。本研究的目的是在统一致死的恒河猴模型中进一步表征埃博拉病毒病，以支持按照严格质量标准开发一个特征明确的模型。将恒河猴通过肌肉注射暴露于埃博拉病毒，一组在预定时间点实施安乐死以表征疾病进展。第二组未安排安乐死，以便分析存活情况、生理变化、临床病理学、终末期病理学和遥测动力学。在第3天，观察到散发性病毒血症，并在淋巴结中发现病理证据。到第5天，在所有暴露于埃博拉病毒的动物中检测到病毒血症，并在肝脏、脾脏和胃肠道组织中发现病理证据。这些数据支持这样一种观点，即在压缩的时间尺度下，恒河猴中的埃博拉病毒感染是一种与人类感染相似的快速全身性疾病。观察到在感染最早阶段与疾病进展相关的生物标志物，从而确定了可用于治疗研究的潜在“触发治疗”指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2d6/7996724/506e8403ed1f/microorganisms-09-00489-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2d6/7996724/58f9ae0bedab/microorganisms-09-00489-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2d6/7996724/cf46764d979e/microorganisms-09-00489-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2d6/7996724/62f947bff672/microorganisms-09-00489-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2d6/7996724/6d7f740451b8/microorganisms-09-00489-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2d6/7996724/a1a173494af9/microorganisms-09-00489-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2d6/7996724/973607bf5327/microorganisms-09-00489-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2d6/7996724/65f8a289855e/microorganisms-09-00489-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2d6/7996724/5700d1419093/microorganisms-09-00489-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2d6/7996724/506e8403ed1f/microorganisms-09-00489-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2d6/7996724/58f9ae0bedab/microorganisms-09-00489-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2d6/7996724/cf46764d979e/microorganisms-09-00489-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2d6/7996724/62f947bff672/microorganisms-09-00489-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2d6/7996724/6d7f740451b8/microorganisms-09-00489-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2d6/7996724/a1a173494af9/microorganisms-09-00489-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2d6/7996724/973607bf5327/microorganisms-09-00489-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2d6/7996724/65f8a289855e/microorganisms-09-00489-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2d6/7996724/5700d1419093/microorganisms-09-00489-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2d6/7996724/506e8403ed1f/microorganisms-09-00489-g009.jpg

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