Riera Elena, Pérez-Núñez Daniel, García-Belmonte Raquel, Miorin Lisa, García-Sastre Adolfo, Revilla Yolanda
Microbes in Health and Welfare Department, Centro de Biología Molecular Severo Ochoa, CSIC-UAM, c/Nicolás Cabrera, Madrid, Spain.
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Front Microbiol. 2021 Aug 26;12:722952. doi: 10.3389/fmicb.2021.722952. eCollection 2021.
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.
非洲猪瘟病毒（ASFV）可在家猪和野猪中引发严重疾病，目前正在全球范围内蔓延。目前尚无针对ASFV的安全有效的疫苗，这对全球养猪业构成了威胁。非洲猪瘟病毒（ASFV）是一种复杂的双链DNA病毒，它展现出多种机制来对抗宿主的先天免疫反应，其效果可能决定了减毒和强毒ASFV毒株所表现出的不同程度的毒力。在此我们报告，强毒的Arm/07/CBM/c2株和减毒的NH/P68株感染均可通过对抗JAK/STAT途径，阻止干扰素（IFN）处理的细胞中干扰素刺激基因（ISG）的表达。这种抑制导致干扰素刺激基因因子3（ISGF3）复合物的核转位受损，以及蛋白酶体依赖性的STAT2降解和半胱天冬酶3依赖性的STAT1裂解。对JAK/STAT途径存在两种独立的控制机制，这表明阻止该途径对于病毒成功复制至关重要。由于ASFV毒力可能与IFN信号抑制机制的效果相关，更好地理解这些IFN拮抗特性可能会带来控制这种毁灭性猪病的新策略。
