Virulence ( IF 5.5 ) Pub Date : 2021-08-02 , DOI: 10.1080/21505594.2021.1935613 Elisa Fanunza 1 , Fabrizio Carletti 2 , Marina Quartu 3 , Nicole Grandi 1 , Laura Ermellino 1 , Jessica Milia 1 , Angela Corona 1 , Maria Rosaria Capobianchi 2 , Giuseppe Ippolito 2 , Enzo Tramontano 1
ABSTRACT
The Interferon (IFN) response is crucial to restrain pathogenic infections. Investigations into flavivirus-host interactions reported that the high virulence is linked to innate immune evasion. Zika Virus (ZIKV) has developed diversified strategies to evade the innate immune system. We report that the viral protein NS2A counteracts the IFN response by strongly suppressing the IFN signaling. NS2A targets transcription factors STAT1 and STAT2, to impede their nuclear localization, thereby suppressing the transcription of ISRE promoter and IFN-stimulated genes. We found that NS2A promotes degradation of STAT1 and STAT2. Treatment of NS2A transfected cells with MG132 restores the levels of both transcription factors, suggesting the involvement of the proteasome system. Given the impact that the IFN antagonism has on flavivirus virulence, the knowledge gained by characterizing the mechanism through which ZIKV evades the IFN response paves the ground for new strategies to attenuate the pathogenesis and to develop countermeasures against effective pharmacological targets.
中文翻译:
寨卡病毒 NS2A 通过降解 STAT1 和 STAT2 抑制干扰素信号传导
摘要
干扰素 (IFN) 反应对于抑制致病性感染至关重要。对黄病毒-宿主相互作用的调查报告说,高毒力与先天免疫逃避有关。寨卡病毒 (ZIKV) 已开发出多种策略来逃避先天免疫系统。我们报告病毒蛋白NS2A 通过强烈抑制干扰素信号来抵消干扰素反应。NS2A 靶向转录因子 STAT1 和 STAT2,以阻止它们的核定位,从而抑制 ISRE 启动子和 IFN 刺激基因的转录。我们发现 NS2A 促进 STAT1 和 STAT2 的降解。用 MG132 处理 NS2A 转染细胞恢复了两种转录因子的水平,表明蛋白酶体系统的参与。鉴于 IFN 拮抗剂对黄病毒毒力的影响,