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体外减毒和强毒非洲猪瘟病毒感染肺泡巨噬细胞后的激活模式。

Patterns of alveolar macrophage activation upon attenuated and virulent African swine fever viruses in vitro.

机构信息

Yerevan State Medical University, Yerevan, Armenia.

Laboratory of Cell Biology and Virology, Institute of Molecular Biology of NAS RA, Yerevan, Armenia.

出版信息

Comp Immunol Microbiol Infect Dis. 2020 Oct;72:101513. doi: 10.1016/j.cimid.2020.101513. Epub 2020 Jun 16.

DOI:10.1016/j.cimid.2020.101513
PMID:32569898
Abstract

The pattern of porcine alveolar macrophage (AM) activation upon classical stimuli of two strains of African swine fever (ASF) viruses, an attenuated ASFV-BA71V and virulent ASFV-Georgia2007 were investigated. In an in vitro experiment ASFV-Georgia2007-infected AM showed M1 polarization pattern different from the one induced by classical stimuli. Altered morphology, appearance of binuclear cells, decreased synthesis of IFN-alpha as well as IFN-epsilon was observed compared with attenuated ASFV-BA71V, and decreased synthesis of IFN-omega compared with intact cells. However, CD68 level did not significantly differ between alveolar macrophage populations infected by ASFV-Georgia2007 and control group, while both LPS/IFN-gamma stimulation and non-pathogenic ASFV-BA71V virus increased the level of CD68 soluble receptor. AM infection with ASFV-Georgia2007 resulted in remarkable DNA proliferation whereas LPS/IFN-gamma and ASFV-BA71V induced less expressed DNA proliferation in activated cells. The higher value of nitric oxide was obvious in the cells infected with ASFV-BA71V, compared to ASFV-Georgia2007 and LPS/IFN-gamma activated cells. In conclusion, pattern of activation of alveolar macrophages induced by ASFV-Georgia2007 virus differs from the one expressed in LPS/IFN-gamma- and ASFV-BA71V-activated cells. ASFV-BA71V and LPS/IFN-gamma share similar antiviral response of porcine AM. Therefore we assume that wild type virulent ASFV can partially down regulate antiviral response of AM and conclude that evolutionary decrease of virulence in ASFV is related to alterations of control of the host cell antiviral response.

摘要

研究了两种非洲猪瘟(ASF)病毒——弱毒 ASFV-BA71V 和强毒 ASFV-Georgia2007 对猪肺泡巨噬细胞(AM)的经典刺激作用下的激活模式。在体外实验中,与弱毒 ASFV-BA71V 诱导的模式不同,ASFV-Georgia2007 感染的 AM 显示出 M1 极化模式。与弱毒 ASFV-BA71V 相比,观察到形态改变、双核细胞出现、IFN-α和 IFN-epsilon 的合成减少,与完整细胞相比,IFN-omega 的合成减少。然而,与感染 ASFV-Georgia2007 的肺泡巨噬细胞群和对照组相比,CD68 水平没有显著差异,而 LPS/IFN-γ刺激和非致病性 ASFV-BA71V 病毒均增加了 CD68 可溶性受体的水平。ASFV-Georgia2007 感染 AM 导致显著的 DNA 增殖,而 LPS/IFN-γ和 ASFV-BA71V 诱导激活细胞中较少表达的 DNA 增殖。与 ASFV-Georgia2007 和 LPS/IFN-γ激活的细胞相比,在感染 ASFV-BA71V 的细胞中,明显观察到更高的一氧化氮值。总之,ASFV-Georgia2007 病毒诱导的肺泡巨噬细胞激活模式与 LPS/IFN-γ和 ASFV-BA71V 激活细胞中表达的模式不同。ASFV-BA71V 和 LPS/IFN-γ共享猪 AM 的相似抗病毒反应。因此,我们假设野生型强毒 ASFV 可以部分下调 AM 的抗病毒反应,并得出结论,ASFV 毒力的进化降低与宿主细胞抗病毒反应控制的改变有关。

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