Ma Zexu, Yu Ying, Xiao Yueqiang, Opriessnig Tanja, Wang Rong, Yang Liping, Nan Yuchen, Samal Siba K, Halbur Patrick G, Zhang Yan-Jin
Molecular Virology Laboratory, VA-MD College of Veterinary Medicine and Maryland Pathogen Research Institute, University of Maryland, College Park, MD, USA.
Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, USA.
J Gen Virol. 2017 Jul;98(7):1720-1729. doi: 10.1099/jgv.0.000819. Epub 2017 Jul 13.
Porcine reproductive and respiratory syndrome virus (PRRSV) is known to antagonize the innate immune response. An atypical PRRSV strain A2MC2 is capable of inducing synthesis of type I interferons (IFNs) in cultured cells. Here, we show that the middle half of the A2MC2 genome is needed for triggering the IFN synthesis. First, a cDNA infectious clone of this atypical strain was constructed as a DNA-launched version. Virus recovery was achieved from the infectious clone and the recovered virus, rA2MC2, was characterized. The rA2MC2 retained the feature of IFN induction in cultured cells. Infection of pigs with the rA2MC2 virus caused viremia similar to that of the wild-type virus. Chimeric infectious clones were constructed by swapping genomic fragments with a cDNA clone of a moderately virulent strain VR-2385 that antagonizes IFN induction. Analysis of the rescued chimeric viruses demonstrated that the middle two fragments, ranging from nt4545 to nt12709 of the A2MC2 genome, were needed for the IFN induction, whereas the chimeric viruses containing any one of the two A2MC2 fragments failed to do so. The results and the cDNA infectious clone of the IFN-inducing A2MC2 will facilitate further study of its biology, ultimately leading towards the development of an improved vaccine against PRRS.
猪繁殖与呼吸综合征病毒（PRRSV）已知会拮抗先天免疫反应。一种非典型PRRSV毒株A2MC2能够在培养细胞中诱导I型干扰素（IFN）的合成。在此，我们表明A2MC2基因组的中间一半对于触发IFN合成是必需的。首先，构建了该非典型毒株的cDNA感染性克隆作为DNA启动版本。从感染性克隆中实现了病毒拯救，并对拯救出的病毒rA2MC2进行了表征。rA2MC2在培养细胞中保留了诱导IFN的特性。用rA2MC2病毒感染猪会引起类似于野生型病毒的病毒血症。通过将基因组片段与一种拮抗IFN诱导的中等毒力毒株VR - 2385的cDNA克隆进行交换，构建了嵌合感染性克隆。对拯救出的嵌合病毒的分析表明，A2MC2基因组中从nt4545到nt12709的中间两个片段对于IFN诱导是必需的，而包含这两个A2MC2片段中任何一个的嵌合病毒都无法做到这一点。诱导IFN的A2MC2的结果和cDNA感染性克隆将有助于对其生物学特性进行进一步研究，最终推动针对PRRS的改进疫苗的开发。
