SARS-CoV-2 virus NSP14 Impairs NRF2/HMOX1 activation by targeting Sirtuin 1

作     者：Shilei Zhang Jingfeng Wang Lulan Wang Saba Aliyari Genhong Cheng Shilei Zhang;Jingfeng Wang;Lulan Wang;Saba Aliyari;Genhong Cheng

作者机构：Department of MicrobiologyImmunologyand Molecular GeneticsUniversity of CaliforniaLos AngelesLos Angeles90095CAUSA 

出 版 物：《Cellular & Molecular Immunology》 (中国免疫学杂志（英文版）)

年 卷 期：2022年第19卷第8期

页      面：872-882页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：National Institute of Health(NIH)grants(AI069120,AI158154 and AI149718) the UCLA AIDS Institute and UCLA David Geffen School of Medicine-Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research Award Program 

主　　题：SARS-CoV-2 NRF2 HMOX1 NSP14 SIRT1 Oxidative stress 

摘      要：Most deaths from the COVID-19 pandemic are due to acute respiratory distress syndrome(ARDS)-related respiratory *** storms and oxidative stress are the major players in ARDS development during respiratory virus ***,it is still unknown how oxidative stress is regulated by viral and host factors in response to SARS-CoV-2 ***,we found that activation of NRF2/HMOX1 significantly suppressed SARS-CoV-2 replication in multiple cell types by producing the metabolite biliverdin,whereas SARS-CoV-2 impaired the NRF2/HMOX1 axis through the action of the nonstructural viral protein ***,NSP14 interacts with the catalytic domain of the NAD-dependent deacetylase Sirtuin 1(SIRT1)and inhibits its ability to activate the NRF2/HMOX1 ***,both genetic and pharmaceutical evidence corroborated the novel antiviral activity of SIRT1 against ***,our findings reveal a novel mechanism by which SARS-CoV-2 dysregulates the host antioxidant defense system and emphasize the vital role played by the SIRT1/NRF2 axis in host defense against SARS-CoV-2.