Attenuated Interferon and Proinflammatory Response in SARS-CoV-2–Infected Human Dendritic Cells Is Associated With Viral Antagonism of STAT1 Phosphorylation. (21st June 2020)

• Record Type: Journal Article
• Authors: Yang, Dong; Chu, Hin; Hou, Yuxin; Chai, Yue; Shuai, Huiping; Lee, Andrew Chak-Yiu; Zhang, Xi; Wang, Yixin; Hu, Bingjie; Huang, Xiner; Yuen, Terrence Tsz-Tai; Cai, Jian-Piao; Zhou, Jie; Yuan, Shuofeng; Zhang, Anna Jinxia; Chan, Jasper Fuk-Woo; Yuen, Kwok-Yung
• Is Part Of: Journal of infectious diseases. Volume 222:Number 5(2020)
• Page Start: 734
• Page End: 745
• Publication Date: 2020-06-21
• Subjects: COVID-19 -- SARS-CoV-2 -- coronavirus -- dendritic cells -- macrophages -- moDCs -- MDMs; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiaa356
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract: Clinical manifestations of coronavirus disease 2019 (COVID-19) vary from asymptomatic virus shedding, nonspecific pharyngitis, to pneumonia with silent hypoxia and respiratory failure. Dendritic cells and macrophages are sentinel cells for innate and adaptive immunity that affect the pathogenesis of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). The interplay between SARS-CoV-2 and these cell types remains unknown. We investigated infection and host responses of monocyte-derived dendritic cells (moDCs) and macrophages (MDMs) infected by SARS-CoV-2. MoDCs and MDMs were permissive to SARS-CoV-2 infection and protein expression but did not support productive virus replication. Importantly, SARS-CoV-2 launched an attenuated interferon response in both cell types and triggered significant proinflammatory cytokine/chemokine expression in MDMs but not moDCs. Investigations suggested that this attenuated immune response to SARS-CoV-2 in moDCs was associated with viral antagonism of STAT1 phosphorylation. These findings may explain the mild and insidious course of COVID-19 until late deterioration. Abstract : MoDCs and MDMs were permissive to SARS-CoV-2 infection but not replication. The virus did not trigger IFN response in either cell type. The attenuated interferon and proinflammatory response in SARS-CoV-2–infected moDCs was associated with viral antagonism of STAT1 phosphorylation.