Evolution of enhanced innate immune evasion by SARS-CoV-2

作     者：Lucy G Thorne 

作者机构：Division of Infection and Immunity University College London London WC1E 6BT United Kingdom Quantitative Biosciences Institute (QBI) Coronavirus Research Group (QCRG) San Francisco CA 94158 USA Global Health and Emerging Pathogens Institute Icahn School of Medicine at Mount Sinai New York NY 10029 USA Quantitative Biosciences Institute (QBI) University of California San Francisco San Francisco CA 94158 USA J. David Gladstone Institutes San Francisco CA 94158 USA Department of Cellular and Molecular Pharmacology University of California San Francisco San Francisco CA 94158 USA Howard Hughes Medical Institute San Francisco CA 94158 USA Division of Advanced Therapies National Institute for Biological Standards and Control South Mimms UK Cardiovascular Research Institute University of California - San Francisco San Francisco CA 94158 USA Division of Virology Department of Pathology University of Cambridge Addenbrooke’s Hospital Hills Road Cambridge CB2 2QQ UK Epithelial Stem Cell Biology & Regenerative Medicine laboratory The Francis Crick Institute 1 Midland Road London NW1 1AT UK Institute of Immunity & Transplantation Division of Infection & Immunity UCL Pears Building London NW3 2PF UK MIT Computer Science and Artificial Intelligence Laboratory Cambridge MA 02139 USA Broad Institute of MIT and Harvard Cambridge MA 02142 USA European Molecular Biology Laboratory (EMBL) European Bioinformatics Institute Wellcome Genome Campus Hinxton Cambridge UK Department of Microbiology Icahn School of Medicine at Mount Sinai New York NY 10029 USA The Tisch Cancer Institute Icahn School of Medicine at Mount Sinai New York NY 10029 USA Department of Medicine Division of Infectious Diseases Icahn School of Medicine at Mount Sinai New York NY 10029 USA Department of Pathology Molecular and Cell-Based Medicine Icahn School of Medicine at Mount Sinai New York NY 10029 USA 

出 版 物：《四川生理科学杂志》 (Sichuan Journal of Physiological Sciences)

年 卷 期：2021年第43卷第10期

页      面：1695-1695页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：Assessment of Transmission and Contagiousness of COVID-19 CF Trust, (896014, SRC006, SRC020) Marie Skłodowska-Curie National Institute of Health Research Health Protection Research Unit Senhwa Biosciences UKRI G2P-UK National Virology consortium, (MR/W005611/1) Vir Biotechnology National Institutes of Health, NIH, (R01GM133981) U.S. Department of Defense, DOD National Cancer Institute, NCI, (F32CA239333, U54CA260560) National Institute of Allergy and Infectious Diseases, NIAID, (75N93021C00014, HHSN272201400008C, P01AI063302, P50AI150476, R01AI120694, R01AI143292, U19AI135972, U19AI135990) Defense Advanced Research Projects Agency, DARPA, (HR0011-19-2-0020) Pfizer F. Hoffmann-La Roche JPB Foundation, JPBF, (2020-215611 (5384)) University of California, San Francisco, UCSF, (133122P) Roddenberry Foundation Wellcome Trust, WT, (108079, 108183, 206298, 207498, 220863, 223065) Manchester Biomedical Research Centre, BRC Medical Research Council, MRC National Institute for Health Research, NIHR, (200927) University College London, UCL, (207511, COVID-19) European Research Council, ERC, (639429) Rosetrees Trust, (M553) National Health Research Institutes, NHRI Agencia de Innovación y Desarrollo de Andalucía, IDEA UCLH Biomedical Research Centre, NIHR BRC 

主　　题：outside likely alone 

摘      要：Emergence of SARS-CoV-2 variants of concern(VOCs)suggests viral adaptation to enhance human-to-human transmission1,*** much effort has focused on characterisation of spike changes in VOCs,mutations outside spike likely contribute to *** we used unbiased abundance proteomics,phosphoproteomics,RNAseq and viral replication assays to show that isolates of the Alpha(B.1.1.7)variant3 more effectively suppress innate immune responses in airway epithelial cells,compared to first wave *** found that Alpha has dramatically increased subgenomic RNA and protein levels of N,Orf9b and Orf6,all known innate immune *** of Orf9b alone suppressed the innate immune response through interaction with TOM70,a mitochondrial protein required for RNA sensing adaptor MAVS ***,the activity of Orf9b and its association with TOM70 was regulated by *** propose that more effective innate immune suppression,through enhanced expression of specific viral antagonist proteins,increases the likelihood of successful Alpha transmission,and may increase in vivo replication and duration of *** importance of mutations outside Spike in adaptation of SARS-CoV-2 to humans is underscored by the observation that similar mutations exist in the Delta and Omicron N/Orf9b regulatory regions.