Virulence and genotype-associated infectivity of interferon-treated macrophages by porcine reproductive and respiratory syndrome viruses
Virulence and genotype-associated infectivity of interferon-treated macrophages by porcine reproductive and respiratory syndrome viruses
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DOI：
10.1016/j.virusres.2013.08.009
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发表时间：
2014-01-22
期刊：
影响因子：
5
通讯作者：
Summerfield, Artur
中科院分区：
文献类型：
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作者：
Garcia-Nicolas, Obdulio;Baumann, Arnaud;Summerfield, Artur
M_1和M_2巨噬细胞(M_(Phi))的极化对于理解M_(Phi)的功能是必不可少的。因此，本研究的目的是确定干扰素-γ(M1)、白介素4(M2)和干扰素-β激活M-Phi对不同毒力的猪生殖呼吸综合征(PRRS)病毒(PRRSV)1型和2型的易感性的影响。为此，在72小时内培养产生单核细胞来源的M-phi，然后加入干扰素-γ、IL-4或干扰素-β诱导极化24小时。M型Phi感染了一组属于基因1和基因2的PRRSV，未分化株和M2型MPhi对所有分离株高度敏感。相反，M1和干扰素-β激活的M-Phi对低致病性1型PRRSV株有抵抗力，但对2型PRRSV株不耐药或仅部分耐药。有趣的是，这两种基因类型的高毒力PRRSV分离株在M1和干扰素-β处理的M Phi中表现出比原型病毒更高的感染水平(P<；0.05)。这在核衣壳表达、病毒滴度和病毒诱导的细胞死亡水平上都可以看到。总之，通过使用干扰素-γ和干扰素-β刺激的Mphi，有可能区分不同的基因和毒力的PRRSV。基因2型PRRSV毒株在逃避I型和II型IFN诱导的内在抗病毒效应方面更有效。我们的体外模型将有助于识别与毒力有关的病毒遗传元件，这一信息不仅对了解PRRS的发病机制很重要，而且对于合理的疫苗设计也很重要。我们的结果还表明，单核细胞来源的M Phi。可作为PRRSV感染模型，代替肺泡型Mphi，避免了猪的死亡。(C)2013爱思唯尔B.V.保留所有权利。
The polarization into M1 and M2 macrophages (M Phi)) is essential to understand M Phi function. Consequently, the aim of this study was to determine the impact of IFN-gamma (M1), IL-4 (M2) and IFN-beta activation of M Phi on the susceptibility to genotype 1 and 2 porcine reproductive respiratory syndrome (PRRS) virus (PRRSV) strains varying in virulence. To this end, monocyte-derived M Phi were generated by culture during 72 h and polarization was induced for another 24 h by addition of IFN-gamma, IL-4 or IFN-beta. M Phi were infected with a collection of PRRSV isolates belonging to genotype 1 and genotype 2. Undifferentiated and M2 M Phi were highly susceptible to all PRRSV isolates. In contrast, M1 and IFN-beta activated M Phi were resistant to low pathogenic genotype 1 PRRSV but not or only partially to genotype 2 PRRSV strains. Interestingly, highly virulent PRRSV isolates of both genotypes showed particularly high levels of infection compared with the prototype viruses in both M1 and IFN-beta-treated M Phi (P < 0.05). This was seen at the level of nucleocapsid expression, viral titres and virus-induced cell death. In conclusion, by using IFN-gamma and IFN-beta stimulated M Phi it is possible to discriminate between PRRSV varying in genotype and virulence. Genotype 2 PRRSV strains are more efficient at escaping the intrinsic antiviral effects induced by type I and II IFNs. Our in vitro model will help to identify viral genetic elements responsible for virulence, an information important not only to understand PRRS pathogenesis but also for a rational vaccine design. Our results also suggest that monocyte-derived M Phi. can be used as a PRRSV infection model instead of alveolar M Phi, avoiding the killing of pigs. (C) 2013 Elsevier B.V. All rights reserved.