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源自毛里塔尼亚的两株裂谷热病毒野外毒株的比较研究

Comparative study of two Rift Valley fever virus field strains originating from Mauritania.

作者信息

Chabert Mehdi, Lacôte Sandra, Marianneau Philippe, Confort Marie-Pierre, Aurine Noémie, Pédarrieu Aurélie, Doumbia Baba, Ould Baba Ould Gueya Mohamed, Habiboullah Habiboullah, Beyatt Ahmed Bezeid El Mamy, Lo Modou Moustapha, Nichols Jenna, Sreenu Vattipally B, da Silva Filipe Ana, Colle Marie-Anne, Pain Bertrand, Cêtre-Sossah Catherine, Arnaud Frédérick, Ratinier Maxime

机构信息

IVPC UMR754, INRAE, Universite Claude Bernard Lyon 1, EPHE, Université PSL, Lyon, France.

CIRAD, UMR ASTRE, Montpellier Cedex, France.

出版信息

PLoS Negl Trop Dis. 2024 Dec 9;18(12):e0012728. doi: 10.1371/journal.pntd.0012728. eCollection 2024 Dec.

Abstract

Rift Valley fever (RVF) is one of the major viral arthropod-borne diseases in Africa. In recent decades, RVF virus (RVFV), the causative agent of RVF, has been responsible for multiple outbreaks in West Africa with important consequences on human and animal health. In particular, an outbreak occurred in 2010 after heavy rains in the desertic region of Adrar, Mauritania. It was characterized by the appearance of severe clinical signs among dromedary camels. Another one occurred in 2013-2014 across Senegal and the southern part of Mauritania. In this study, we characterized two RVFV field strains isolated during these two outbreaks. The first strain, MRU25010-30, was isolated from a camel (2010) while the second, MRU2687-3, was isolated from a goat (2013). By deep-sequencing and rapid amplification of cDNA-ends by polymerase chain reaction, we successfully sequenced the complete genome of these two RVFV strains as well as the reference laboratory strain ZH548. Phylogenetic analysis showed that the two field viruses belong to two different RVFV genetic lineages. Moreover, we showed that MRU25010-30 replicates more efficiently in various in vitro cell culture models than MRU2687-3 and ZH548. In vivo, MRU25010-30 caused rapid death of BALB/c mice and proved to be more virulent than MRU2687-3, regardless of the route of inoculation (subcutaneous or intranasal). The virulence of MRU25010-30 is associated with a high viral load in the liver and serum of infected mice, while the death of mice infected with MRU2687-3 and ZH548 correlated with a high viral load in the brain. Altogether, the data presented in this study provide new avenues to unveil the molecular viral determinants that modulate RVFV virulence and replication capacity.

摘要

裂谷热(RVF)是非洲主要的病毒性节肢动物传播疾病之一。近几十年来,裂谷热的病原体裂谷热病毒(RVFV)在西非引发了多次疫情,对人类和动物健康造成了重大影响。特别是2010年,在毛里塔尼亚阿德拉尔沙漠地区暴雨过后爆发了疫情。其特征是单峰骆驼出现严重临床症状。另一次疫情于2013 - 2014年在塞内加尔和毛里塔尼亚南部爆发。在本研究中,我们对在这两次疫情期间分离出的两株RVFV野外毒株进行了特征分析。第一株毒株MRU25010 - 30于2010年从一头骆驼身上分离得到,而第二株毒株MRU2687 - 3于2013年从一只山羊身上分离得到。通过深度测序和聚合酶链反应对cDNA末端进行快速扩增,我们成功测定了这两株RVFV毒株以及参考实验室毒株ZH548的完整基因组序列。系统发育分析表明,这两株野外病毒属于两个不同的RVFV遗传谱系。此外,我们发现MRU25010 - 30在各种体外细胞培养模型中的复制效率高于MRU2687 - 3和ZH548。在体内,MRU25010 - 30导致BALB/c小鼠迅速死亡,并且无论接种途径(皮下或鼻内)如何,都证明其比MRU2687 - 3更具毒性。MRU25010 - 30的毒性与感染小鼠肝脏和血清中的高病毒载量相关,而感染MRU2687 - 3和ZH548的小鼠死亡与大脑中的高病毒载量相关。总之,本研究提供的数据为揭示调节RVFV毒力和复制能力的分子病毒决定因素提供了新途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8d2/11658707/0ef28e94730a/pntd.0012728.g001.jpg

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