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非人灵长类动物中的埃博拉病毒感染受到暴露材料中糖蛋白多聚-U编辑位点群体的时间影响。

Ebola Virus Infections in Nonhuman Primates Are Temporally Influenced by Glycoprotein Poly-U Editing Site Populations in the Exposure Material.

作者信息

Trefry John C, Wollen Suzanne E, Nasar Farooq, Shamblin Joshua D, Kern Steven J, Bearss Jeremy J, Jefferson Michelle A, Chance Taylor B, Kugelman Jeffery R, Ladner Jason T, Honko Anna N, Kobs Dean J, Wending Morgan Q S, Sabourin Carol L, Pratt William D, Palacios Gustavo F, Pitt M Louise M

机构信息

Virology Division, US Army Medical Research Institute for Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA.

Pathology Division, U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA.

出版信息

Viruses. 2015 Dec 19;7(12):6739-54. doi: 10.3390/v7122969.

Abstract

Recent experimentation with the variants of the Ebola virus that differ in the glycoprotein's poly-uridine site, which dictates the form of glycoprotein produced through a transcriptional stutter, has resulted in questions regarding the pathogenicity and lethality of the stocks used to develop products currently undergoing human clinical trials to combat the disease. In order to address these concerns and prevent the delay of these critical research programs, we designed an experiment that permitted us to intramuscularly challenge statistically significant numbers of naïve and vaccinated cynomolgus macaques with either a 7U or 8U variant of the Ebola virus, Kikwit isolate. In naïve animals, no difference in survivorship was observed; however, there was a significant delay in the disease course between the two groups. Significant differences were also observed in time-of-fever, serum chemistry, and hematology. In vaccinated animals, there was no statistical difference in survivorship between either challenge groups, with two succumbing in the 7U group compared to 1 in the 8U challenge group. In summary, survivorship was not affected, but the Ebola virus disease course in nonhuman primates is temporally influenced by glycoprotein poly-U editing site populations.

摘要

最近对埃博拉病毒变体进行的实验中,这些变体在糖蛋白的多聚尿苷位点存在差异,该位点决定了通过转录口吃产生的糖蛋白形式,这引发了有关用于开发目前正在进行人体临床试验以对抗该疾病的产品的病毒株的致病性和致死性的问题。为了解决这些担忧并防止这些关键研究项目的延迟,我们设计了一项实验,使我们能够用埃博拉病毒基奎特毒株的7U或8U变体对数量具有统计学意义的未感染和已接种疫苗的食蟹猴进行肌肉注射攻击。在未感染的动物中,未观察到存活率的差异;然而,两组之间的病程存在显著延迟。在发热时间、血清化学和血液学方面也观察到了显著差异。在已接种疫苗的动物中,两个攻击组之间的存活率没有统计学差异,7U组有两只死亡,而8U攻击组有一只死亡。总之,存活率未受影响,但非人类灵长类动物的埃博拉病毒病程在时间上受糖蛋白多聚-U编辑位点群体的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d999/4690892/c9bbb549a1fa/viruses-07-02969-g001.jpg

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