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Comprehensive Comparison of RNA-Seq Data of SARS-CoV-2, SARS-CoV and MERS-CoV Infections: Alternative Entry Routes and Innate Immune Responses.
Front Immunol. 2021; 12:656433.FI

Abstract

Background

The pathogenesis of COVID-19 emerges as complex, with multiple factors leading to injury of different organs. Some of the studies on aspects of SARS-CoV-2 cell entry and innate immunity have produced seemingly contradictory claims. In this situation, a comprehensive comparative analysis of a large number of related datasets from several studies could bring more clarity, which is imperative for therapy development.

Methods

We therefore performed a comprehensive comparative study, analyzing RNA-Seq data of infections with SARS-CoV-2, SARS-CoV and MERS-CoV, including data from different types of cells as well as COVID-19 patients. Using these data, we investigated viral entry routes and innate immune responses.

Results and Conclusion

First, our analyses support the existence of cell entry mechanisms for SARS and SARS-CoV-2 other than the ACE2 route with evidence of inefficient infection of cells without expression of ACE2; expression of TMPRSS2/TPMRSS4 is unnecessary for efficient SARS-CoV-2 infection with evidence of efficient infection of A549 cells transduced with a vector expressing human ACE2. Second, we find that innate immune responses in terms of interferons and interferon simulated genes are strong in relevant cells, for example Calu3 cells, but vary markedly with cell type, virus dose, and virus type.

Authors+Show Affiliations

Bioinformatics and Computational Biophysics, Faculty of Biology and Center for Medical Biotechnology (ZMB), University of Duisburg-Essen, Essen, Germany.Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Shanghai, China.Bioinformatics and Computational Biophysics, Faculty of Biology and Center for Medical Biotechnology (ZMB), University of Duisburg-Essen, Essen, Germany.Department of Dermatology, University Hospital Essen, Essen, Germany. Department of Translational Skin Cancer Research (TSCR), German Cancer Consortium (DKTK), Partner Site Essen, German Cancer Research Center, Heidelberg, Germany.Bioinformatics and Computational Biophysics, Faculty of Biology and Center for Medical Biotechnology (ZMB), University of Duisburg-Essen, Essen, Germany.Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Shanghai, China.Bioinformatics and Computational Biophysics, Faculty of Biology and Center for Medical Biotechnology (ZMB), University of Duisburg-Essen, Essen, Germany.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34122413

Citation

Cao, Yingying, et al. "Comprehensive Comparison of RNA-Seq Data of SARS-CoV-2, SARS-CoV and MERS-CoV Infections: Alternative Entry Routes and Innate Immune Responses." Frontiers in Immunology, vol. 12, 2021, p. 656433.
Cao Y, Xu X, Kitanovski S, et al. Comprehensive Comparison of RNA-Seq Data of SARS-CoV-2, SARS-CoV and MERS-CoV Infections: Alternative Entry Routes and Innate Immune Responses. Front Immunol. 2021;12:656433.
Cao, Y., Xu, X., Kitanovski, S., Song, L., Wang, J., Hao, P., & Hoffmann, D. (2021). Comprehensive Comparison of RNA-Seq Data of SARS-CoV-2, SARS-CoV and MERS-CoV Infections: Alternative Entry Routes and Innate Immune Responses. Frontiers in Immunology, 12, 656433. https://doi.org/10.3389/fimmu.2021.656433
Cao Y, et al. Comprehensive Comparison of RNA-Seq Data of SARS-CoV-2, SARS-CoV and MERS-CoV Infections: Alternative Entry Routes and Innate Immune Responses. Front Immunol. 2021;12:656433. PubMed PMID: 34122413.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comprehensive Comparison of RNA-Seq Data of SARS-CoV-2, SARS-CoV and MERS-CoV Infections: Alternative Entry Routes and Innate Immune Responses. AU - Cao,Yingying, AU - Xu,Xintian, AU - Kitanovski,Simo, AU - Song,Lina, AU - Wang,Jun, AU - Hao,Pei, AU - Hoffmann,Daniel, Y1 - 2021/05/28/ PY - 2021/01/20/received PY - 2021/04/06/accepted PY - 2021/6/14/entrez PY - 2021/6/15/pubmed PY - 2021/7/6/medline KW - IFNs KW - ISGs KW - MERS-CoV KW - SARS-CoV KW - SARS-CoV-2 KW - innate immune response KW - virus entry route SP - 656433 EP - 656433 JF - Frontiers in immunology JO - Front Immunol VL - 12 N2 - Background: The pathogenesis of COVID-19 emerges as complex, with multiple factors leading to injury of different organs. Some of the studies on aspects of SARS-CoV-2 cell entry and innate immunity have produced seemingly contradictory claims. In this situation, a comprehensive comparative analysis of a large number of related datasets from several studies could bring more clarity, which is imperative for therapy development. Methods: We therefore performed a comprehensive comparative study, analyzing RNA-Seq data of infections with SARS-CoV-2, SARS-CoV and MERS-CoV, including data from different types of cells as well as COVID-19 patients. Using these data, we investigated viral entry routes and innate immune responses. Results and Conclusion: First, our analyses support the existence of cell entry mechanisms for SARS and SARS-CoV-2 other than the ACE2 route with evidence of inefficient infection of cells without expression of ACE2; expression of TMPRSS2/TPMRSS4 is unnecessary for efficient SARS-CoV-2 infection with evidence of efficient infection of A549 cells transduced with a vector expressing human ACE2. Second, we find that innate immune responses in terms of interferons and interferon simulated genes are strong in relevant cells, for example Calu3 cells, but vary markedly with cell type, virus dose, and virus type. SN - 1664-3224 UR - https://www.unboundmedicine.com/medline/citation/34122413/Comprehensive_Comparison_of_RNA_Seq_Data_of_SARS_CoV_2_SARS_CoV_and_MERS_CoV_Infections:_Alternative_Entry_Routes_and_Innate_Immune_Responses_ DB - PRIME DP - Unbound Medicine ER -