Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, Avenida da Universidade Técnica, 1300-477 Lisboa, Portugal.
Vet Microbiol. 2018 Mar;216:132-141. doi: 10.1016/j.vetmic.2018.02.008. Epub 2018 Feb 7.
ASFV causes an important disease of domestic swine and wild boar. Currently no vaccine is available, highlighting the necessity to understand ASFV modulation of innate immune responses in natural host cells. With this aim, macrophage cultures enriched in SWC9 and CD163 differentiation markers were infected in parallel with high virulent ASFV/L60 and low virulent ASFV/NHV, the latter lacking MGF 360 and 505/530 genes associated with type I interferon (IFN I) control. IFN I production and signaling were studied after completion of the viral cycles. None of the viruses increased IFN I production in host cells, and accordingly, didn't cause activation of the central mediator of the pathway IRF3. However, upon stimulation by poly:IC treatment during infections, L60 and NHV similarly inhibited IFN I production. This didn't seem to depend on IRF3 modulation since its activation levels were not significantly decreased in L60 infection and were even increased in NHV's, in comparison to stimulated mock infections. The infections didn't evidently activate JAK-STAT pathway mediators STAT1 and STAT2, but did increase expression of interferon stimulated genes (ISGs), to higher levels in NHV than L60 infection. Interestingly, in presence of IFN-α, L60 but not NHV was able to decrease significantly the expression of some of the ISGs tested. Overall, both L60 and NHV were able to inhibit IFN I production in macrophages, through a mechanism not dependent on IRF3 modulation. The high virulent isolate showed however a more effective control of the downstream ISGs expression pathway.
ASFV 引起家猪和野猪的重要疾病。目前尚无可用的疫苗，这突出表明有必要了解 ASFV 对天然宿主细胞固有免疫反应的调节。为此，用高毒力 ASFV/L60 和低毒力 ASFV/NHV 平行感染富含 SWC9 和 CD163 分化标志物的巨噬细胞培养物，后者缺乏与 I 型干扰素 (IFN I) 控制相关的 MGF 360 和 505/530 基因。病毒周期完成后研究了 IFN I 的产生和信号转导。没有一种病毒能增加宿主细胞中的 IFN I 产生，因此不会导致该途径的中心介质 IRF3 的激活。然而，在用 poly：IC 处理刺激感染时，L60 和 NHV 同样抑制了 IFN I 的产生。这似乎并不依赖于 IRF3 的调节，因为 L60 感染中其激活水平没有显著降低，而在 NHV 中甚至增加，与刺激的模拟感染相比。感染并未明显激活 JAK-STAT 途径介质 STAT1 和 STAT2，但确实增加了干扰素刺激基因 (ISGs) 的表达，在 NHV 中的表达水平高于 L60 感染。有趣的是，在 IFN-α存在下，L60 但不是 NHV 能够显著降低所测试的一些 ISGs 的表达。总体而言，L60 和 NHV 均能够抑制巨噬细胞中 IFN I 的产生，其机制不依赖于 IRF3 的调节。然而，高毒力分离株对下游 ISGs 表达途径的控制更为有效。
