Abstract
African swine fever virus (ASFV) causes a serious disease in domestic pigs and wild boars and is currently expanding worldwide. No safe and efficacious vaccines against ASFV are available, which threats the swine industry worldwide. African swine fever virus (ASFV) is a complex dsDNA virus that displays multiple mechanisms to counteract the host innate immune response, whose efficacy might determine the different degrees of virulence displayed by attenuated and virulent ASFV strains. Here we report that infection with both virulent Arm/07/CBM/c2 and attenuated NH/P68 strains prevents interferon-stimulated gene (ISG) expression in interferon (IFN)-treated cells by counteracting the JAK/STAT pathway. This inhibition results in an impaired nuclear translocation of the interferon-stimulated gene factor 3 (ISGF3) complex, as well as in the proteasome-dependent STAT2 degradation and caspase 3-dependent STAT1 cleavage. The existence of two independent mechanisms of control of the JAK/STAT pathway, suggests the importance of preventing this pathway for successful viral replication. As ASFV virulence is likely associated with the efficacy of the IFN signaling inhibitory mechanisms, a better understanding of these IFN antagonistic properties may lead to new strategies to control this devastating pig disease.
Highlights
African swine fever virus (ASFV) is the causative agent of African swine fever (ASF) disease, which affects domestic pigs and wild boars (Viñuela, 1985)
We previously described that the virulent ASFV Arm/07 strain, but not the attenuated NH/P68 strain, inhibits IFN-β production by blocking the cGAS-STING pathway in porcine alveolar macrophages (PAM) (García-Belmonte et al, 2019)
To further demonstrate that NH/P68 and Arm/07/CBM/c2 viruses are able to counteract the IFN-I signaling pathway, we assessed the IFN-dependent activity of the interferonstimulated response element (ISRE) promoter in mock infected or ASFV infected COS-1 cells by performing a Dual-Luciferase reporter gene assay (Figures 1B,C)
Summary
African swine fever virus (ASFV) is the causative agent of African swine fever (ASF) disease, which affects domestic pigs and wild boars (Viñuela, 1985). Depending on the virulence of the viral strain, disease manifestations include chronical or subclinical forms as well as acute hemorrhagic forms (Gómez-Villamandos et al, 2013) that can result in death of the infected hosts in few days (Blome et al, 2013). Despite the disease was eradicated from Europe in 1995, the 2007 outbreak in the Caucasus resulted in the spreading of the virus to neighboring countries including Russia and more recently Bulgaria, Belgium and Germany, with more than 500 outbreaks reported up to date in Europe. The tropism of the virus is generally restricted to cells of the monocyte-macrophage lineage (Viñuela, 1985; Gómez-Villamandos et al, 2013). These cells are crucial players in the host defense against infection and constitute one of the key effectors of the innate immune response. The establishment of successful innate immunity evasion strategies may be required to initiate a productive infection
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