气候变化领域集成服务门户(CCPortal): Sars-cov-2 induces double-stranded rna-mediated innate immune responses in respiratory epithelial-derived cells and cardiomyocytes

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DOI	10.1073/PNAS.2022643118
	Sars-cov-2 induces double-stranded rna-mediated innate immune responses in respiratory epithelial-derived cells and cardiomyocytes
	Li Y.; Renner D.M.; Comar C.E.; Whelan J.N.; Reyes H.M.; Cardenas-Diaz F.L.; Truitt R.; Tan L.H.; Dong B.; Alysandratos K.D.; Huang J.; Palmer J.N.; Adappa N.D.; Kohanski M.A.; Kotton D.N.; Silverman R.H.; Yang W.; Morrisey E.E.; Cohen N.A.; Weiss S.R.
发表日期	2021
ISSN	00278424
卷号	118 期号:16
英文摘要	Coronaviruses are adept at evading host antiviral pathways induced by viral double-stranded RNA, including interferon (IFN) signaling, oligoadenylate synthetase-ribonuclease L (OAS-RNase L), and protein kinase R (PKR). While dysregulated or inadequate IFN responses have been associated with severe coronavirus infection, the extent to which the recently emerged SARS-CoV-2 activates or antagonizes these pathways is relatively unknown. We found that SARS-CoV-2 infects patient-derived nasal epithelial cells, present at the initial site of infection; induced pluripotent stem cell-derived alveolar type 2 cells (iAT2), the major cell type infected in the lung; and cardiomyocytes (iCM), consistent with cardiovascular consequences of COVID- 19 disease. Robust activation of IFN or OAS-RNase L is not observed in these cell types, whereas PKR activation is evident in iAT2 and iCM. In SARS-CoV-2-infected Calu-3 and A549ACE2 lung-derived cell lines, IFN induction remains relatively weak; however, activation of OAS-RNase L and PKR is observed. This is in contrast to Middle East respiratory syndrome (MERS)-CoV, which effectively inhibits IFN signaling and OAS-RNase L and PKR pathways, but is similar to mutant MERS-CoV lacking innate immune antagonists. Remarkably, OASRNase L and PKR are activated in MAVS knockout A549ACE2 cells, demonstrating that SARS-CoV-2 can induce these host antiviral pathways despite minimal IFN production. Moreover, increased replication and cytopathic effect in RNASEL knockout A549ACE2 cells implicates OASRNase L in restricting SARS-CoV-2. Finally, while SARS-CoV-2 fails to antagonize these host defense pathways, which contrasts with other coronaviruses, the IFN signaling response is generally weak. These host-virus interactions may contribute to the unique pathogenesis of SARS-CoV-2. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Interferon; Interferon signaling genes; OAS-RNase L; PKR; SARS-CoV-2
语种	英语
scopus关键词	2-5A-dependent ribonuclease; double stranded RNA; protein kinase R; ribonuclease; A-549 cell line; cardiac muscle cell; epithelium cell; human; immunology; innate immunity; lung; metabolism; Middle East respiratory syndrome coronavirus; nose; pathology; physiology; virology; virus replication; A549 Cells; eIF-2 Kinase; Endoribonucleases; Epithelial Cells; Humans; Immunity, Innate; Lung; Middle East Respiratory Syndrome Coronavirus; Myocytes, Cardiac; Nose; RNA, Double-Stranded; SARS-CoV-2; Virus Replication
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180030
作者单位	Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States; Penn Center for Research on Coronaviruses and Other Emerging Pathogens, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States; Penn-CHOP Lung Biology Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States; Institute for Regenerative Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States; Department of Otorhinolaryngology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States; Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, United States; Department of Medicine, The Pulmonary Center, Center for Regenerative Medicine, Boston Universit...
推荐引用方式 GB/T 7714	Li Y.,Renner D.M.,Comar C.E.,et al. Sars-cov-2 induces double-stranded rna-mediated innate immune responses in respiratory epithelial-derived cells and cardiomyocytes[J],2021,118(16).
APA	Li Y..,Renner D.M..,Comar C.E..,Whelan J.N..,Reyes H.M..,...&Weiss S.R..(2021).Sars-cov-2 induces double-stranded rna-mediated innate immune responses in respiratory epithelial-derived cells and cardiomyocytes.Proceedings of the National Academy of Sciences of the United States of America,118(16).
MLA	Li Y.,et al."Sars-cov-2 induces double-stranded rna-mediated innate immune responses in respiratory epithelial-derived cells and cardiomyocytes".Proceedings of the National Academy of Sciences of the United States of America 118.16(2021).