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通过裂谷热静脉病毒MP-12疫苗株进行种间重配的风险分析。

Risk analysis of inter-species reassortment through a Rift Valley fever phlebovirus MP-12 vaccine strain.

作者信息

Ly Hoai J, Lokugamage Nandadeva, Nishiyama Shoko, Ikegami Tetsuro

机构信息

Department of Pathology, The University of Texas Medical Branch, Galveston, Texas, United States of America.

Sealy Center for Vaccine Development, The University of Texas Medical Branch, Galveston, Texas, United States of America.

出版信息

PLoS One. 2017 Sep 19;12(9):e0185194. doi: 10.1371/journal.pone.0185194. eCollection 2017.

Abstract

Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to Africa and the Arabian Peninsula. The causative agent, Rift Valley fever phlebovirus (RVFV), belongs to the genus Phlebovirus in the family Phenuiviridae and causes high rates of abortions in ruminants, and hemorrhagic fever, encephalitis, or blindness in humans. Viral maintenance by mosquito vectors has led to sporadic RVF outbreaks in ruminants and humans in endemic countries, and effective vaccination of animals and humans may minimize the impact of this disease. A live-attenuated MP-12 vaccine strain is one of the best characterized RVFV strains, and was conditionally approved as a veterinary vaccine in the U.S. Live-attenuated RVF vaccines including MP-12 strain may form reassortant strains with other bunyavirus species. This study thus aimed to characterize the occurrence of genetic reassortment between the MP-12 strain and bunyavirus species closely related to RVFV. The Arumowot virus (AMTV) and Gouleako goukovirus (GOLV), are transmitted by mosquitoes in Africa. The results of this study showed that GOLV does not form detectable reassortant strains with the MP-12 strain in co-infected C6/36 cells. The AMTV also did not form any reassortant strains with MP-12 strain in co-infected C6/36 cells, due to the incompatibility among N, L, and Gn/Gc proteins. A lack of reassortant formation could be due to a functional incompatibility of N and L proteins derived from heterologous species, and due to a lack of packaging via heterologous Gn/Gc proteins. The MP-12 strain did, however, randomly exchange L-, M-, and S-segments with a genetic variant strain, rMP12-GM50, in culture cells. The MP-12 strain is thus unlikely to form any reassortant strains with AMTV or GOLV in nature.

摘要

裂谷热(RVF)是一种由蚊子传播的人畜共患病,在非洲和阿拉伯半岛流行。病原体裂谷热静脉病毒(RVFV)属于白蛉病毒科白蛉病毒属,可导致反刍动物高流产率,以及人类出血热、脑炎或失明。蚊子媒介维持病毒导致流行国家的反刍动物和人类中不时爆发裂谷热,对动物和人类进行有效疫苗接种可将这种疾病的影响降至最低。减毒活疫苗MP-12毒株是特征最明确的RVFV毒株之一,在美国被有条件批准为兽用疫苗。包括MP-12毒株在内的减毒活裂谷热疫苗可能与其他布尼亚病毒属物种形成重配毒株。因此,本研究旨在确定MP-12毒株与与RVFV密切相关的布尼亚病毒属物种之间基因重配的发生情况。阿鲁莫沃特病毒(AMTV)和古莱阿科古科病毒(GOLV)在非洲由蚊子传播。本研究结果表明,在共感染的C6/36细胞中,GOLV不会与MP-12毒株形成可检测到的重配毒株。由于N、L和Gn/Gc蛋白之间不兼容,AMTV在共感染的C6/36细胞中也不会与MP-12毒株形成任何重配毒株。缺乏重配毒株的形成可能是由于来自异源物种的N和L蛋白功能不兼容,以及缺乏通过异源Gn/Gc蛋白进行包装。然而,在培养细胞中,MP-12毒株确实与一个基因变异毒株rMP12-GM50随机交换了L、M和S片段。因此,MP-12毒株在自然界中不太可能与AMTV或GOLV形成任何重配毒株。

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