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非洲马瘟病毒血清型4和9在IFNAR(-/-)、Balb/C和129 Sv/Ev小鼠中的毒力研究。

Study of the virulence of serotypes 4 and 9 of African horse sickness virus in IFNAR(-/-), Balb/C and 129 Sv/Ev mice.

作者信息

de la Grandière Maria Ana, Dal Pozzo Fabiana, Tignon Marylène, Zonta William, Thiry Damien, Mauroy Axel, Mathijs Élisabeth, Caij Ann Brigitte, Saegerman Claude, Thiry Étienne

机构信息

Veterinary Virology and Animal Viral Diseases, Fundamental and Applied Research on Animal and Health (FARAH), Faculty of Veterinary Medicine, University of Liège, B-4000 Liège, Belgium.

Research Unit of Epidemiology and Risk Analysis Applied to Veterinary Sciences (UREAR-ULg), Fundamental and Applied Research on Animal and Health (FARAH), Faculty of Veterinary Medicine, University of Liège, B-4000 Liège, Belgium.

出版信息

Vet Microbiol. 2014 Dec 5;174(3-4):322-332. doi: 10.1016/j.vetmic.2014.10.006. Epub 2014 Oct 23.

DOI:10.1016/j.vetmic.2014.10.006
PMID:25458420
Abstract

African horse sickness virus (AHSV) is a double-stranded RNA virus which belongs to the family Reoviridae, genus Orbivirus. Recent studies have focused on the interferon-α/β receptor knock-out mice (IFNAR(-/-)) as a small animal laboratory for the development of AHSV vaccines. The aim of this work was to study in vivo the virulence of two strains of AHSV and to compare the outcome of the infection of three mouse strains. To address this, AHSV serotypes 4 (AHSV-4) and 9 (AHSV-9) were inoculated subcutaneously (SC) and intranasally (IN) in two immunocompetent mouse strains (Balb/C and 129 Sv/Ev (129 WT)) as well as IFNAR(-/-) mice (on 129 Sv/Ev genetic background). In IFNAR(-/-) mice, fatality up to 50% was measured and significantly more clinical signs were observed in comparison with SC inoculated immunocompetent mice. The observed clinical signs were significantly more severe after AHSV-4 infection, in particular in immunocompetent mice inoculated by IN route. Considering RNAemia, significantly higher viral loads were measured following AHSV-4 infection. In the organs of 129 WT inoculated by IN route, significantly higher viral loads were detected after AHSV-4 infection. Together the results support a higher virulence for AHSV-4 compared to AHSV-9 and a higher clinical impact following infections in IN inoculated mice, at least in the investigated strains. The study also brought indirect evidences for type I IFN involvement in the control of AHSV infection.

摘要

非洲马瘟病毒(AHSV)是一种双链RNA病毒,属于呼肠孤病毒科环状病毒属。最近的研究聚焦于将α/β干扰素受体敲除小鼠(IFNAR(-/-))作为开发AHSV疫苗的小型动物实验模型。这项工作的目的是在体内研究两株AHSV的毒力,并比较三种小鼠品系感染后的结果。为此,将AHSV血清型4(AHSV-4)和9(AHSV-9)分别皮下(SC)和鼻内(IN)接种到两种免疫健全的小鼠品系(Balb/C和129 Sv/Ev(129 WT))以及IFNAR(-/-)小鼠(129 Sv/Ev遗传背景)中。在IFNAR(-/-)小鼠中,测得的死亡率高达50%,与皮下接种的免疫健全小鼠相比,观察到明显更多的临床症状。AHSV-4感染后观察到的临床症状明显更严重,尤其是经鼻内途径接种的免疫健全小鼠。考虑到病毒血症,AHSV-4感染后测得的病毒载量明显更高。在经鼻内途径接种的129 WT小鼠的器官中,AHSV-4感染后检测到明显更高的病毒载量。总体而言,这些结果支持AHSV-4比AHSV-9具有更高的毒力,并且在经鼻内接种的小鼠感染后具有更大的临床影响,至少在所研究的品系中如此。该研究还间接证明了I型干扰素参与AHSV感染的控制。

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