Nasal ciliated cells are primary targets for SARS-CoV-2 replication in early stage of COVID-19
The upper respiratory tract is compromised in the early period of COVID-19, but SARS-CoV-2 tropism at the cellular level is not fully defined. Unlike recent single cell RNA-sequencing analyses indicating uniformly low mRNA expression of SARS-CoV-2 entry-related host molecules in all nasal epithelial...
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Veröffentlicht in: | The Journal of clinical investigation 2021-07, Vol.131 (13), p.1-14 |
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creator | Ahn, Ji Hoon Kim, JungMo Hong, Seon Pyo Choi, Sung Yong Yang, Myung Jin Ju, Young Seok Kim, Young Tae Kim, Ho Min Rahman, M D Tazikur Chung, Man Ki Hong, Sang Duk Bae, Hosung Lee, Chang-Seop Koh, Gou Young |
description | The upper respiratory tract is compromised in the early period of COVID-19, but SARS-CoV-2 tropism at the cellular level is not fully defined. Unlike recent single cell RNA-sequencing analyses indicating uniformly low mRNA expression of SARS-CoV-2 entry-related host molecules in all nasal epithelial cells, we show that the protein levels are relatively high and their localizations are restricted to the apical side of multiciliated epithelial cells. In addition, we provide evidence in COVID-19 patients that SARS-CoV-2 is massively detected and replicated within the multiciliated cells. We observed these findings during the early stage of COVID-19, when infected ciliated cells are rapidly replaced by differentiating precursor cells. Moreover, our analyses reveal that SARS-CoV-2 cellular tropism is restricted to the nasal ciliated versus oral squamous epithelium. These results imply that targeting ciliated cells of the nasal epithelium during the early stage of COVID-19 could be an ideal strategy to prevent SARS-CoV-2 propagation. |
doi_str_mv | 10.1172/jci148517 |
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Unlike recent single cell RNA-sequencing analyses indicating uniformly low mRNA expression of SARS-CoV-2 entry-related host molecules in all nasal epithelial cells, we show that the protein levels are relatively high and their localizations are restricted to the apical side of multiciliated epithelial cells. In addition, we provide evidence in COVID-19 patients that SARS-CoV-2 is massively detected and replicated within the multiciliated cells. We observed these findings during the early stage of COVID-19, when infected ciliated cells are rapidly replaced by differentiating precursor cells. Moreover, our analyses reveal that SARS-CoV-2 cellular tropism is restricted to the nasal ciliated versus oral squamous epithelium. These results imply that targeting ciliated cells of the nasal epithelium during the early stage of COVID-19 could be an ideal strategy to prevent SARS-CoV-2 propagation.</description><identifier>ISSN: 1558-8238</identifier><identifier>ISSN: 0021-9738</identifier><identifier>EISSN: 1558-8238</identifier><identifier>DOI: 10.1172/jci148517</identifier><identifier>PMID: 34003804</identifier><language>eng</language><publisher>United States: American Society for Clinical Investigation</publisher><subject>Biomedical research ; Cell differentiation ; Coronaviruses ; COVID-19 ; Disease transmission ; Epithelial cells ; Epithelium ; Gene expression ; Genetic aspects ; Health aspects ; Infections ; Localization ; Lungs ; Pathogens ; Proteins ; Respiratory tract ; Severe acute respiratory syndrome coronavirus 2 ; Tropism ; Viruses</subject><ispartof>The Journal of clinical investigation, 2021-07, Vol.131 (13), p.1-14</ispartof><rights>COPYRIGHT 2021 American Society for Clinical Investigation</rights><rights>Copyright American Society for Clinical Investigation Jul 2021</rights><rights>2021 American Society for Clinical Investigation 2021 American Society for Clinical Investigation</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c713t-824cc8ae72c0802f7731acb81b49911308799bbca365bbd0f20f892a28fbb9aa3</citedby><cites>FETCH-LOGICAL-c713t-824cc8ae72c0802f7731acb81b49911308799bbca365bbd0f20f892a28fbb9aa3</cites><orcidid>0000-0001-5848-7972 ; 0000-0002-0122-3105 ; 0000-0002-9923-8099 ; 0000-0001-9006-4881 ; 0000-0003-0029-3643</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245175/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245175/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,315,728,781,785,886,27926,27927,53793,53795</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34003804$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ahn, Ji Hoon</creatorcontrib><creatorcontrib>Kim, JungMo</creatorcontrib><creatorcontrib>Hong, Seon Pyo</creatorcontrib><creatorcontrib>Choi, Sung Yong</creatorcontrib><creatorcontrib>Yang, Myung Jin</creatorcontrib><creatorcontrib>Ju, Young Seok</creatorcontrib><creatorcontrib>Kim, Young Tae</creatorcontrib><creatorcontrib>Kim, Ho Min</creatorcontrib><creatorcontrib>Rahman, M D Tazikur</creatorcontrib><creatorcontrib>Chung, Man Ki</creatorcontrib><creatorcontrib>Hong, Sang Duk</creatorcontrib><creatorcontrib>Bae, Hosung</creatorcontrib><creatorcontrib>Lee, Chang-Seop</creatorcontrib><creatorcontrib>Koh, Gou Young</creatorcontrib><title>Nasal ciliated cells are primary targets for SARS-CoV-2 replication in early stage of COVID-19</title><title>The Journal of clinical investigation</title><addtitle>J Clin Invest</addtitle><description>The upper respiratory tract is compromised in the early period of COVID-19, but SARS-CoV-2 tropism at the cellular level is not fully defined. Unlike recent single cell RNA-sequencing analyses indicating uniformly low mRNA expression of SARS-CoV-2 entry-related host molecules in all nasal epithelial cells, we show that the protein levels are relatively high and their localizations are restricted to the apical side of multiciliated epithelial cells. In addition, we provide evidence in COVID-19 patients that SARS-CoV-2 is massively detected and replicated within the multiciliated cells. We observed these findings during the early stage of COVID-19, when infected ciliated cells are rapidly replaced by differentiating precursor cells. Moreover, our analyses reveal that SARS-CoV-2 cellular tropism is restricted to the nasal ciliated versus oral squamous epithelium. These results imply that targeting ciliated cells of the nasal epithelium during the early stage of COVID-19 could be an ideal strategy to prevent SARS-CoV-2 propagation.</description><subject>Biomedical research</subject><subject>Cell differentiation</subject><subject>Coronaviruses</subject><subject>COVID-19</subject><subject>Disease transmission</subject><subject>Epithelial cells</subject><subject>Epithelium</subject><subject>Gene expression</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Infections</subject><subject>Localization</subject><subject>Lungs</subject><subject>Pathogens</subject><subject>Proteins</subject><subject>Respiratory tract</subject><subject>Severe acute respiratory syndrome coronavirus 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Unlike recent single cell RNA-sequencing analyses indicating uniformly low mRNA expression of SARS-CoV-2 entry-related host molecules in all nasal epithelial cells, we show that the protein levels are relatively high and their localizations are restricted to the apical side of multiciliated epithelial cells. In addition, we provide evidence in COVID-19 patients that SARS-CoV-2 is massively detected and replicated within the multiciliated cells. We observed these findings during the early stage of COVID-19, when infected ciliated cells are rapidly replaced by differentiating precursor cells. Moreover, our analyses reveal that SARS-CoV-2 cellular tropism is restricted to the nasal ciliated versus oral squamous epithelium. 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subjects | Biomedical research Cell differentiation Coronaviruses COVID-19 Disease transmission Epithelial cells Epithelium Gene expression Genetic aspects Health aspects Infections Localization Lungs Pathogens Proteins Respiratory tract Severe acute respiratory syndrome coronavirus 2 Tropism Viruses |
title | Nasal ciliated cells are primary targets for SARS-CoV-2 replication in early stage of COVID-19 |
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