{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T15:37:19Z","timestamp":1790869039044,"version":"4.1.0"},"reference-count":89,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,5,28]],"date-time":"2021-05-28T00:00:00Z","timestamp":1622160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2021.656433","type":"journal-article","created":{"date-parts":[[2021,5,28]],"date-time":"2021-05-28T10:12:17Z","timestamp":1622196737000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Comprehensive Comparison of RNA-Seq Data of SARS-CoV-2, SARS-CoV and MERS-CoV Infections: Alternative Entry Routes and Innate Immune Responses"],"prefix":"10.3389","volume":"12","author":[{"given":"Yingying","family":"Cao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xintian","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simo","family":"Kitanovski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Hoffmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,5,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/S0065-3527(06)66005-3","article-title":"The Molecular Biology of Coronaviruses","volume":"66","author":"Masters","year":"2006","journal-title":"Adv Virus Res"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-virology-100114-055218","article-title":"Continuous and Discontinuous Rna Synthesis in Coronaviruses","volume":"2","author":"Sola","year":"2015","journal-title":"Annu Rev Virol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-1-4939-2438-7_1","article-title":"Coronaviruses: An Overview of Their Replication and Pathogenesis","volume":"1282","author":"Fehr","year":"2015","journal-title":"Coronaviruses"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)13967-0","article-title":"Newly Discovered Coronavirus as the Primary Cause of Severe Acute Respiratory Syndrome","volume":"362","author":"Kuiken","year":"2003","journal-title":"Lancet"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1211721","article-title":"Isolation of a Novel Coronavirus From a Man With Pneumonia in Saudi Arabia","volume":"367","author":"Zaki","year":"2012","journal-title":"N Engl J Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2008-3","article-title":"A New Coronavirus Associated With Human Respiratory Disease in China","volume":"579","author":"Wu","year":"2020","journal-title":"Nature"},{"key":"B7","doi-asserted-by":"publisher","first-page":"135","DOI":"10.3390\/v12020135","article-title":"Return of the Coronavirus: 2019-Ncov","volume":"12","author":"Gralinski","year":"2020","journal-title":"Viruses"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1007\/s11427-020-1637-5","article-title":"Evolution of the Novel Coronavirus From the Ongoing Wuhan Outbreak and Modeling of its Spike Protein for Risk of Human Transmission","volume":"63","author":"Xu","year":"2020","journal-title":"Sci China Life Sci"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2020.07.040","article-title":"Physical Distancing, Face Masks, and Eye Protection to Prevent Person-to-Person Transmission of Sars-Cov-2 and covid-19: A Systematic Review and Meta-Analysis","volume":"395","author":"Chu","year":"2020","journal-title":"Lancet"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(20)30074-7","article-title":"Feasibility of Controlling covid-19 Outbreaks by Isolation of Cases and Contacts","volume":"8","author":"Hellewell","year":"2020","journal-title":"Lancet Global Health"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32007-9","article-title":"Lessons Learnt From Easing covid-19 Restrictions: An Analysis of Countries and Regions in Asia Pacific and Europe","volume":"396","author":"Han","year":"2020","journal-title":"Lancet"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD013574","article-title":"Quarantine Alone or in Combination With Other Public Health Measures to Control covid-19: A Rapid Review","author":"Nussbaumer-Streit","year":"2020","journal-title":"Cochrane Database Systematic Rev"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(20)30843-4","article-title":"Safety, Tolerability, and Immunogenicity of an Inactivated Sars-Cov-2 Vaccine in Healthy Adults Aged 18\u201359 Years: A Randomised, Double-Blind, Placebo-Controlled, Phase 1\/2 Clinical Trial","volume":"21","author":"Zhang","year":"2021","journal-title":"Lancet Infect Dis"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2022483","article-title":"An Mrna Vaccine Against sars-cov-2\u2014preliminary Report","volume":"383","author":"Jackson","year":"2020","journal-title":"N Engl J Med"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/s40506-015-0048-2","article-title":"Therapeutic Options for Middle East Respiratory Syndrome Coronavirus (Mers-Cov) Infection: How Close are We","volume":"7","author":"Omrani","year":"2015","journal-title":"Curr Treat Options Infect Dis"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.2217\/fvl.12.126","article-title":"Development of Sars Vaccines and Therapeutics is Still Needed","volume":"8","author":"Jiang","year":"2013","journal-title":"Future Virol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s43440-020-00204-0","article-title":"Sars-Cov-2 Therapeutics: How Far do We Stand From a Remedy","author":"Singh","year":"2021","journal-title":"Pharmacol Rep"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3390\/v4061011","article-title":"Mechanisms of Coronavirus Cell Entry Mediated by the Viral Spike Protein","volume":"4","author":"Belouzard","year":"2012","journal-title":"Viruses"},{"key":"B19","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.tips.2013.11.006","article-title":"Current Progress in Antiviral Strategies","volume":"35","author":"Lou","year":"2014","journal-title":"Trends Pharmacol Sci"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3390\/molecules16010221","article-title":"Targeting Cell Entry of Enveloped Viruses as an Antiviral Strategy","volume":"16","author":"Teissier","year":"2011","journal-title":"Molecules"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2020.05.012","article-title":"Sars-Cov-2 Entry in Host Cells-Multiple Targets for Treatment and Prevention","volume":"175","author":"Mahmoud","year":"2020","journal-title":"Biochimie"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.20095","article-title":"The Life Cycle of Sars Coronavirus in Vero E6 Cells","volume":"73","author":"Qinfen","year":"2004","journal-title":"J Med Virol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.02.052","article-title":"Sars-Cov-2 Cell Entry Depends on Ace2 and Tmprss2 and is Blocked by a Clinically Proven Protease Inhibitor","volume":"181","author":"Hoffmann","year":"2020","journal-title":"Cell"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.11.5642-5650.2004","article-title":"Ph-Dependent Entry of Severe Acute Respiratory Syndrome Coronavirus is Mediated by the Spike Glycoprotein and Enhanced by Dendritic Cell Transfer Through Dc-Sign","volume":"78","author":"Yang","year":"2004","journal-title":"J Virol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1038\/cr.2008.15","article-title":"Sars Coronavirus Entry Into Host Cells Through a Novel Clathrin-and Caveolae-Independent Endocytic Pathway","volume":"18","author":"Wang","year":"2008","journal-title":"Cell Res"},{"key":"B26","doi-asserted-by":"publisher","first-page":"280","DOI":"10.3390\/v11030280","article-title":"Host Determinants of Mers-Cov Transmission and Pathogenesis","volume":"11","author":"Widagdo","year":"2019","journal-title":"Viruses"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-virology-110615-042301","article-title":"Structure, Function, and Evolution of Coronavirus Spike Proteins","volume":"3","author":"Li","year":"2016","journal-title":"Annu Rev Virol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"108175","DOI":"10.1016\/j.celrep.2020.108175","article-title":"A Single-Cell Rna Expression Map of Human Coronavirus Entry Factors","volume":"32","author":"Singh","year":"2020","journal-title":"Cell Rep"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1101\/2021.03.01.433431","article-title":"Systematic Analysis of Sars-Cov-2 Infection of an ace2-negative Human Airway Cell","author":"Puray-Chavez","year":"2021","journal-title":"bioRxiv"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1101\/2020.03.14.988345","article-title":"Sars-Cov-2 Invades Host Cells Via a Novel Route: Cd147-spike Protein","author":"Wang","year":"2020","journal-title":"bioRxiv"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1101\/2020.06.22.165803","article-title":"Cd209l\/l-sign and cd209\/dc-sign Act as Receptors for Sars-Cov-2 and are Differentially Expressed in Lung and Kidney Epithelial and Endothelial Cells","author":"Amraie","year":"2020","journal-title":"bioRxiv"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-020-00460-y","article-title":"Axl is a Candidate Receptor for Sars-Cov-2 That Promotes Infection of Pulmonary and Bronchial Epithelial Cells","volume":"31","author":"Wang","year":"2021","journal-title":"Cell Res"},{"key":"B33","doi-asserted-by":"publisher","first-page":"e9610","DOI":"10.15252\/msb.20209610","article-title":"The Protein Expression Profile of Ace2 in Human Tissues","volume":"16","author":"Hikmet","year":"2020","journal-title":"Mol Syst Biol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2001737","article-title":"Sars-Cov-2 Viral Load in Upper Respiratory Specimens of Infected Patients","volume":"382","author":"Zou","year":"2020","journal-title":"N Engl J Med"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0306446101","article-title":"Characterization of Severe Acute Respiratory Syndrome-Associated Coronavirus (Sars-Cov) Spike Glycoprotein-Mediated Viral Entry","volume":"101","author":"Simmons","year":"2004","journal-title":"Proc Natl Acad Sci"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abc3582","article-title":"Tmprss2 and Tmprss4 Promote Sars-Cov-2 Infection of Human Small Intestinal Enterocytes","volume":"5","author":"Zang","year":"2020","journal-title":"Sci Immunol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA118.001273","article-title":"Tmprss11a Activates the Influenza a Virus Hemagglutinin and the Mers Coronavirus Spike Protein and is Insensitive Against Blockade by Hai-1","volume":"293","author":"Zmora","year":"2018","journal-title":"J Biol Chem"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2003138117","article-title":"Cell Entry Mechanisms of Sars-Cov-2","volume":"117","author":"Shang","year":"2020","journal-title":"Proc Natl Acad Sci"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-020-15562-9","article-title":"Characterization of Spike Glycoprotein of Sars-Cov-2 on Virus Entry and its Immune Cross-Reactivity With Sars-Cov","volume":"11","author":"Ou","year":"2020","journal-title":"Nat Commun"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.05.003","article-title":"Immune Signaling by Rig-I-Like Receptors","volume":"34","author":"Loo","year":"2011","journal-title":"Immunity"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2004.11.007","article-title":"The Role of Toll-Like Receptors in the Host Response to Viruses","volume":"42","author":"Bowie","year":"2005","journal-title":"Mol Immunol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2006.08.009","article-title":"Type I Inteferon Gene Induction by the Interferon Regulatory Factor Family of Transcription Factors","volume":"25","author":"Honda","year":"2006","journal-title":"Immunity"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/nri2436","article-title":"Viral Evasion and Subversion of Pattern-Recognition Receptor Signalling","volume":"8","author":"Bowie","year":"2008","journal-title":"Nat Rev Immunol"},{"key":"B44","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1038\/ni.1863","article-title":"The Role of Pattern-Recognition Receptors in Innate Immunity: Update on Toll-Like Receptors","volume":"11","author":"Kawai","year":"2010","journal-title":"Nat Immunol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.6.3434","article-title":"Ifn Regulatory Factor Family Members Differentially Regulate the Expression of Type Iii Ifn (Ifn-\u03bb) Genes","volume":"179","author":"\u00d6sterlund","year":"2007","journal-title":"J Immunol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3212","article-title":"Guarding the Frontiers: The Biology of Type Iii Interferons","volume":"16","author":"Wack","year":"2015","journal-title":"Nat Immunol"},{"key":"B47","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.it.2016.10.008","article-title":"Post-Translational Control of Intracellular Pathogen Sensing Pathways","volume":"38","author":"Chiang","year":"2017","journal-title":"Trends Immunol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2020.05.008","article-title":"Type I and Type Iii Interferons\u2013Induction, Signaling, Evasion, and Application to Combat covid-19","volume":"27","author":"Park","year":"2020","journal-title":"Cell Host Microbe"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-020-05991-x","article-title":"Clinical Predictors of Mortality Due to covid-19 Based on an Analysis of Data of 150 Patients From Wuhan, China","volume":"46","author":"Ruan","year":"2020","journal-title":"Intensive Care Med"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)31042-4","article-title":"Triple Combination of Interferon beta-1b, Lopinavir\u2013Ritonavir, and Ribavirin in the Treatment of Patients Admitted to Hospital With covid-19: An Open-Label, Randomised, Phase 2 Trial","volume":"395","author":"Hung","year":"2020","journal-title":"Lancet"},{"key":"B51","doi-asserted-by":"publisher","first-page":"e12465","DOI":"10.15252\/emmm.202012465","article-title":"Covid-19: Lambda Interferon Against Viral Load and Hyperinflammation","volume":"12","author":"Andreakos","year":"2020","journal-title":"EMBO Mol Med"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.04.026","article-title":"Imbalanced Host Response to Sars-Cov-2 Drives Development of covid-19","volume":"181","author":"Blanco-Melo","year":"2020","journal-title":"Cell"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2020.04.017","article-title":"Heightened Innate Immune Responses in the Respiratory Tract of covid-19 Patients","volume":"27","author":"Zhou","year":"2020","journal-title":"Cell Host Microbe"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1126\/science.abc3545","article-title":"Type Iii Interferons Disrupt the Lung Epithelial Barrier Upon Viral Recognition","volume":"369","author":"Broggi","year":"2020","journal-title":"Science"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.2139\/ssrn.3555695","article-title":"Viral Invasion and Type I Interferon Response Characterize the Immunophenotypes During covid-19 Infection","author":"Wei","year":"2020"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-0762-x","article-title":"Single-Cell Landscape of Immunological Responses in Patients With Covid-19","volume":"21","author":"Zhang","year":"2020","journal-title":"Nat Immunol"},{"key":"B57","doi-asserted-by":"publisher","first-page":"104791","DOI":"10.1016\/j.antiviral.2020.104791","article-title":"Type 1 Interferons as a Potential Treatment Against Covid-19","volume":"178","author":"Sallard","year":"2020","journal-title":"Antiviral Res"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1101\/2020.05.05.079194","article-title":"Bulk and Single-Cell Gene Expression Profiling of Sars-Cov-2 Infected Human Cell Lines Identifies Molecular Targets for Therapeutic Intervention","author":"Wyler","year":"2020","journal-title":"bioRxiv"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2020.1747363","article-title":"Transcriptomic Characteristics of Bronchoalveolar Lavage Fluid and Peripheral Blood Mononuclear Cells in covid-19 Patients","volume":"9","author":"Xiong","year":"2020","journal-title":"Emerg Microbes Infect"},{"key":"B60","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-019-13751-9","article-title":"Obesity and Disease Severity Magnify Disturbed Microbiome-Immune Interactions in Asthma Patients","volume":"10","author":"Michalovich","year":"2019","journal-title":"Nat Commun"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0901-9","article-title":"Single-Cell Landscape of Bronchoalveolar Immune Cells in Patients With Covid-19","volume":"26","author":"Liao","year":"2020","journal-title":"Nat Med"},{"key":"B62","doi-asserted-by":"publisher","first-page":"1802441","DOI":"10.1183\/13993003.02441-2018","article-title":"Proliferating spp1\/mertk-expressing Macrophages in Idiopathic Pulmonary Fibrosis","volume":"54","author":"Morse","year":"2019","journal-title":"Eur Respir J"},{"key":"B63","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1471-2164-15-419","article-title":"Comparison of Rna-Seq by Poly (a) Capture, Ribosomal Rna Depletion, and Dna Microarray for Expression Profiling","volume":"15","author":"Zhao","year":"2014","journal-title":"BMC Genomics"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm1000","article-title":"Database Resources of the National Center for Biotechnology Information","volume":"36","author":"Sayers","year":"2008","journal-title":"Nucleic Acids Res"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq967","article-title":"The European Nucleotide Archive","volume":"39","author":"Leinonen","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2577-1","article-title":"Discovery of SARS-CoV-2 Antiviral Drugs Through Large-Scale Compound Repurposing","volume":"586","author":"Riva","year":"2020","journal-title":"Nature"},{"key":"B67","doi-asserted-by":"publisher","first-page":"D24","DOI":"10.1093\/nar\/gkz913","article-title":"Database Resources of the National Genomics Data Center in 2020","volume":"48","author":"Zhang","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz966","article-title":"Ensembl 2020","volume":"48","author":"Yates","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"B69","article-title":"Fastqc: A Quality Control Tool for High Throughput Sequence Data","author":"Andrews","year":"2010"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: A Flexible Trimmer for Illumina Sequence Data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3519","article-title":"Near-Optimal Probabilistic Rna-Seq Quantification","volume":"34","author":"Bray","year":"2016","journal-title":"Nat Biotechnol"},{"key":"B72","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1038\/nmeth.4324","article-title":"Differential Analysis of Rna-Seq Incorporating Quantification Uncertainty","volume":"14","author":"Pimentel","year":"2017","journal-title":"Nat Methods"},{"key":"B73","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1186\/1471-2105-12-480","article-title":"Gc-Content Normalization for Rna-Seq Data","volume":"12","author":"Risso","year":"2011","journal-title":"BMC Bioinf"},{"key":"B74","article-title":"Genome Wide Annotation for Human","volume":"3","author":"Carlson","year":"2017","journal-title":"R Package Version"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btw777","article-title":"Scater: Pre-Processing, Quality Control, Normalization and Visualization of Single-Cell Rna-Seq Data in R","volume":"33","author":"McCarthy","year":"2017","journal-title":"Bioinformatics"},{"key":"B76","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nmeth.1923","article-title":"Fast Gapped-Read Alignment With Bowtie 2","volume":"9","author":"Langmead","year":"2012","journal-title":"Nat Methods"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The Sequence Alignment\/Map Format and Samtools","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"B78","article-title":"Pheatmap: Pretty Heatmaps","author":"Kolde","year":"2019","journal-title":"R Package Version 1.0.12"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btw313","article-title":"Complex Heatmaps Reveal Patterns and Correlations in Multidimensional Genomic Data","volume":"32","author":"Gu","year":"2016","journal-title":"Bioinformatics"},{"key":"B80","doi-asserted-by":"publisher","first-page":"256294","DOI":"10.1155\/2012\/256294","article-title":"Angiotensin-Converting Enzyme 2 (ace2) is a Key Modulator of the Renin Angiotensin System in Health and Disease","volume":"2012","author":"Tikellis","year":"2012","journal-title":"Int J Peptides"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0505577102","article-title":"Inhibitors of Cathepsin L Prevent Severe Acute Respiratory Syndrome Coronavirus Entry","volume":"102","author":"Simmons","year":"2005","journal-title":"Proc Natl Acad Sci"},{"key":"B82","doi-asserted-by":"publisher","first-page":"e105114","DOI":"10.15252\/embj.2020105114","article-title":"Sars-Cov-2 Receptor Ace 2 and Tmprss 2 are Primarily Expressed in Bronchial Transient Secretory Cells","volume":"39","author":"Lukassen","year":"2020","journal-title":"EMBO J"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1101\/2020.05.14.097204","article-title":"Expression of Ace2 and Tmprss2 Proteins in the Upper and Lower Aerodigestive Tracts of Rats","author":"Ueha","year":"2020"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1101\/2020.07.25.221036","article-title":"No Evidence for Basigin\/cd147 as a Direct Sars-Cov-2 Spike Binding Receptor","author":"Shilts","year":"2020"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1038\/ncb0509-510","article-title":"Virus Entry by Macropinocytosis","volume":"11","author":"Mercer","year":"2009","journal-title":"Nat Cell Biol"},{"key":"B86","doi-asserted-by":"publisher","first-page":"104859","DOI":"10.1016\/j.phrs.2020.104859","article-title":"Candidate Drugs Against Sars-Cov-2 and Covid-19","volume":"157","author":"McKee","year":"2020","journal-title":"Pharmacol Res"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-10-4166","article-title":"Chemokine Up-Regulation in Sars-Coronavirus\u2013Infected, Monocyte-Derived Human Dendritic Cells","volume":"106","author":"Law","year":"2005","journal-title":"Blood"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.12.7819-7826.2005","article-title":"Cytokine Responses in Severe Acute Respiratory Syndrome Coronavirus-Infected Macrophages In Vitro: Possible Relevance to Pathogenesis","volume":"79","author":"Cheung","year":"2005","journal-title":"J Virol"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1016\/S1386-6532(03)00195-1","article-title":"Sars-Coronavirus Replicates in Mononuclear Cells of Peripheral Blood (Pbmcs) From Sars Patients","volume":"28","author":"Li","year":"2003","journal-title":"J Clin Virol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.656433\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,28]],"date-time":"2021-05-28T10:12:21Z","timestamp":1622196741000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.656433\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,28]]},"references-count":89,"alternative-id":["10.3389\/fimmu.2021.656433"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.656433","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.01.07.425716","asserted-by":"object"}]},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,28]]},"article-number":"656433"}}