Evaluation of SARS-CoV-2 entry, inflammation and new therapeutics in human lung tissue cells
The development of physiological models that reproduce SARS-CoV-2 infection in primary human cells will be instrumental to identify host-pathogen interactions and potential therapeutics. Here, using cell suspensions directly from primary human lung tissues (HLT), we have developed a rapid platform f...
Gespeichert in:
| Veröffentlicht in: | PLoS pathogens 2022-01, Vol.18 (1), p.e1010171 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 1 |
| container_start_page | e1010171 |
| container_title | PLoS pathogens |
| container_volume | 18 |
| creator | Grau-Expósito, Judith Perea, David Suppi, Marina Massana, Núria Vergara, Ander Soler, Maria José Trinite, Benjamin Blanco, Julià García-Pérez, Javier Alcamí, José Serrano-Mollar, Anna Rosado, Joel Falcó, Vicenç Genescà, Meritxell Buzon, Maria J |
| description | The development of physiological models that reproduce SARS-CoV-2 infection in primary human cells will be instrumental to identify host-pathogen interactions and potential therapeutics. Here, using cell suspensions directly from primary human lung tissues (HLT), we have developed a rapid platform for the identification of viral targets and the expression of viral entry factors, as well as for the screening of viral entry inhibitors and anti-inflammatory compounds. The direct use of HLT cells, without long-term cell culture and in vitro differentiation approaches, preserves main immune and structural cell populations, including the most susceptible cell targets for SARS-CoV-2; alveolar type II (AT-II) cells, while maintaining the expression of proteins involved in viral infection, such as ACE2, TMPRSS2, CD147 and AXL. Further, antiviral testing of 39 drug candidates reveals a highly reproducible method, suitable for different SARS-CoV-2 variants, and provides the identification of new compounds missed by conventional systems, such as VeroE6. Using this method, we also show that interferons do not modulate ACE2 expression, and that stimulation of local inflammatory responses can be modulated by different compounds with antiviral activity. Overall, we present a relevant and rapid method for the study of SARS-CoV-2. |
| doi_str_mv | 10.1371/journal.ppat.1010171 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_2762198596</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A691414933</galeid><doaj_id>oai_doaj_org_article_b990951b70384557affdc96d81fa76d0</doaj_id><sourcerecordid>A691414933</sourcerecordid><originalsourceid>FETCH-LOGICAL-c712t-f42ed71741be4d29b087f790b226a9d12e4857f4d0e77c8e540440dafe7de0963</originalsourceid><addsrcrecordid>eNqVklGL1DAQx4so3nn6DUQLPgl2TdKkaV6EZTl14VC4VZ-EkCaTbpa22Wva0_v2Zm97xxX0QfKQMPnNPzOTf5K8xGiBc47f7_zYd6pZ7PdqWGAUF8ePklPMWJ7xnNPHD84nybMQdghRnOPiaXKSM0SYKPLT5Of5tWpGNTjfpd6mm-XlJlv5HxlJoRv6m3ep62yj2vZIqM6kHfxKhy30ag_j4HSIRLodW9WlzdjV6eBCGCHV0DThefLEqibAi2k_S75_PP-2-pxdfP20Xi0vMs0xGTJLCRiOOcUVUENEhUpuuUAVIYUSBhOgJeOWGgSc6xIYRZQioyxwAyi2cZa8PuruGx_kNJggCS8IFiW7JdZHwni1k_vetaq_kV45eRvwfS1VH7tpQFZCIMFwxVFeUsa4stZoUZgSW8ULg6LWh-m1sWrB6MOgVDMTnd90bitrfy1LLjDlPAq8mQR6fzVCGP5R8kTVKlYVv8FHMd26oOWyiEKYijyP1OIvVFwGWqd9B9bF-Czh7SwhMgP8Hmo1hiDXm8v_YL_MWXpkde9D6MHeDwQjeTDsXZPyYFg5GTamvXo4zPukO4fmfwD5KeW6</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2762198596</pqid></control><display><type>article</type><title>Evaluation of SARS-CoV-2 entry, inflammation and new therapeutics in human lung tissue cells</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>PubMed Central Open Access</source><source>Public Library of Science (PLoS) Journals Open Access</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Grau-Expósito, Judith ; Perea, David ; Suppi, Marina ; Massana, Núria ; Vergara, Ander ; Soler, Maria José ; Trinite, Benjamin ; Blanco, Julià ; García-Pérez, Javier ; Alcamí, José ; Serrano-Mollar, Anna ; Rosado, Joel ; Falcó, Vicenç ; Genescà, Meritxell ; Buzon, Maria J</creator><contributor>Channappanavar, Rudra</contributor><creatorcontrib>Grau-Expósito, Judith ; Perea, David ; Suppi, Marina ; Massana, Núria ; Vergara, Ander ; Soler, Maria José ; Trinite, Benjamin ; Blanco, Julià ; García-Pérez, Javier ; Alcamí, José ; Serrano-Mollar, Anna ; Rosado, Joel ; Falcó, Vicenç ; Genescà, Meritxell ; Buzon, Maria J ; Channappanavar, Rudra</creatorcontrib><description>The development of physiological models that reproduce SARS-CoV-2 infection in primary human cells will be instrumental to identify host-pathogen interactions and potential therapeutics. Here, using cell suspensions directly from primary human lung tissues (HLT), we have developed a rapid platform for the identification of viral targets and the expression of viral entry factors, as well as for the screening of viral entry inhibitors and anti-inflammatory compounds. The direct use of HLT cells, without long-term cell culture and in vitro differentiation approaches, preserves main immune and structural cell populations, including the most susceptible cell targets for SARS-CoV-2; alveolar type II (AT-II) cells, while maintaining the expression of proteins involved in viral infection, such as ACE2, TMPRSS2, CD147 and AXL. Further, antiviral testing of 39 drug candidates reveals a highly reproducible method, suitable for different SARS-CoV-2 variants, and provides the identification of new compounds missed by conventional systems, such as VeroE6. Using this method, we also show that interferons do not modulate ACE2 expression, and that stimulation of local inflammatory responses can be modulated by different compounds with antiviral activity. Overall, we present a relevant and rapid method for the study of SARS-CoV-2.</description><identifier>ISSN: 1553-7374</identifier><identifier>ISSN: 1553-7366</identifier><identifier>EISSN: 1553-7374</identifier><identifier>DOI: 10.1371/journal.ppat.1010171</identifier><identifier>PMID: 35025963</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>ACE2 ; Adult ; Alveoli ; Analysis ; Angiotensin-converting enzyme 2 ; Animals ; Anti-inflammatory agents ; Antiviral activity ; Antiviral agents ; Antiviral Agents - pharmacology ; Antiviral Agents - therapeutic use ; Axl protein ; Biology and life sciences ; CD147 antigen ; Cell culture ; Cell differentiation ; Cell suspensions ; Cells, Cultured ; Chlorocebus aethiops ; Coronaviruses ; COVID-19 ; COVID-19 - immunology ; COVID-19 - pathology ; COVID-19 Drug Treatment ; Dendritic cells ; Dosage and administration ; Drug development ; Drug Evaluation, Preclinical ; Drug resistance ; Drugs, Investigational - pharmacology ; Drugs, Investigational - therapeutic use ; Gene expression ; HEK293 Cells ; Host-pathogen interactions ; Host-Pathogen Interactions - drug effects ; Host-virus relationships ; Humans ; Infection control ; Infections ; Inflammation ; Inflammation - pathology ; Inflammation - therapy ; Inflammation - virology ; Lung - pathology ; Lung - virology ; Lungs ; Medicine and health sciences ; Methods ; Neutrophils ; Nonsteroidal anti-inflammatory drugs ; Phosphatase ; Physiology ; Proteins ; Pulmonary function tests ; Research and Analysis Methods ; SARS-CoV-2 - drug effects ; SARS-CoV-2 - physiology ; Severe acute respiratory syndrome coronavirus 2 ; Thoracic surgery ; Vero Cells ; Viral diseases ; Viral infections ; Virus Internalization - drug effects</subject><ispartof>PLoS pathogens, 2022-01, Vol.18 (1), p.e1010171</ispartof><rights>COPYRIGHT 2022 Public Library of Science</rights><rights>2022 Grau-Expósito et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2022 Grau-Expósito et al 2022 Grau-Expósito et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c712t-f42ed71741be4d29b087f790b226a9d12e4857f4d0e77c8e540440dafe7de0963</citedby><cites>FETCH-LOGICAL-c712t-f42ed71741be4d29b087f790b226a9d12e4857f4d0e77c8e540440dafe7de0963</cites><orcidid>0000-0003-4427-9413</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/PMC8791477/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8791477/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53770,53772,79347,79348</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35025963$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Channappanavar, Rudra</contributor><creatorcontrib>Grau-Expósito, Judith</creatorcontrib><creatorcontrib>Perea, David</creatorcontrib><creatorcontrib>Suppi, Marina</creatorcontrib><creatorcontrib>Massana, Núria</creatorcontrib><creatorcontrib>Vergara, Ander</creatorcontrib><creatorcontrib>Soler, Maria José</creatorcontrib><creatorcontrib>Trinite, Benjamin</creatorcontrib><creatorcontrib>Blanco, Julià</creatorcontrib><creatorcontrib>García-Pérez, Javier</creatorcontrib><creatorcontrib>Alcamí, José</creatorcontrib><creatorcontrib>Serrano-Mollar, Anna</creatorcontrib><creatorcontrib>Rosado, Joel</creatorcontrib><creatorcontrib>Falcó, Vicenç</creatorcontrib><creatorcontrib>Genescà, Meritxell</creatorcontrib><creatorcontrib>Buzon, Maria J</creatorcontrib><title>Evaluation of SARS-CoV-2 entry, inflammation and new therapeutics in human lung tissue cells</title><title>PLoS pathogens</title><addtitle>PLoS Pathog</addtitle><description>The development of physiological models that reproduce SARS-CoV-2 infection in primary human cells will be instrumental to identify host-pathogen interactions and potential therapeutics. Here, using cell suspensions directly from primary human lung tissues (HLT), we have developed a rapid platform for the identification of viral targets and the expression of viral entry factors, as well as for the screening of viral entry inhibitors and anti-inflammatory compounds. The direct use of HLT cells, without long-term cell culture and in vitro differentiation approaches, preserves main immune and structural cell populations, including the most susceptible cell targets for SARS-CoV-2; alveolar type II (AT-II) cells, while maintaining the expression of proteins involved in viral infection, such as ACE2, TMPRSS2, CD147 and AXL. Further, antiviral testing of 39 drug candidates reveals a highly reproducible method, suitable for different SARS-CoV-2 variants, and provides the identification of new compounds missed by conventional systems, such as VeroE6. Using this method, we also show that interferons do not modulate ACE2 expression, and that stimulation of local inflammatory responses can be modulated by different compounds with antiviral activity. Overall, we present a relevant and rapid method for the study of SARS-CoV-2.</description><subject>ACE2</subject><subject>Adult</subject><subject>Alveoli</subject><subject>Analysis</subject><subject>Angiotensin-converting enzyme 2</subject><subject>Animals</subject><subject>Anti-inflammatory agents</subject><subject>Antiviral activity</subject><subject>Antiviral agents</subject><subject>Antiviral Agents - pharmacology</subject><subject>Antiviral Agents - therapeutic use</subject><subject>Axl protein</subject><subject>Biology and life sciences</subject><subject>CD147 antigen</subject><subject>Cell culture</subject><subject>Cell differentiation</subject><subject>Cell suspensions</subject><subject>Cells, Cultured</subject><subject>Chlorocebus aethiops</subject><subject>Coronaviruses</subject><subject>COVID-19</subject><subject>COVID-19 - immunology</subject><subject>COVID-19 - pathology</subject><subject>COVID-19 Drug Treatment</subject><subject>Dendritic cells</subject><subject>Dosage and administration</subject><subject>Drug development</subject><subject>Drug Evaluation, Preclinical</subject><subject>Drug resistance</subject><subject>Drugs, Investigational - pharmacology</subject><subject>Drugs, Investigational - therapeutic use</subject><subject>Gene expression</subject><subject>HEK293 Cells</subject><subject>Host-pathogen interactions</subject><subject>Host-Pathogen Interactions - drug effects</subject><subject>Host-virus relationships</subject><subject>Humans</subject><subject>Infection control</subject><subject>Infections</subject><subject>Inflammation</subject><subject>Inflammation - pathology</subject><subject>Inflammation - therapy</subject><subject>Inflammation - virology</subject><subject>Lung - pathology</subject><subject>Lung - virology</subject><subject>Lungs</subject><subject>Medicine and health sciences</subject><subject>Methods</subject><subject>Neutrophils</subject><subject>Nonsteroidal anti-inflammatory drugs</subject><subject>Phosphatase</subject><subject>Physiology</subject><subject>Proteins</subject><subject>Pulmonary function tests</subject><subject>Research and Analysis Methods</subject><subject>SARS-CoV-2 - drug effects</subject><subject>SARS-CoV-2 - physiology</subject><subject>Severe acute respiratory syndrome coronavirus 2</subject><subject>Thoracic surgery</subject><subject>Vero Cells</subject><subject>Viral diseases</subject><subject>Viral infections</subject><subject>Virus Internalization - drug effects</subject><issn>1553-7374</issn><issn>1553-7366</issn><issn>1553-7374</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqVklGL1DAQx4so3nn6DUQLPgl2TdKkaV6EZTl14VC4VZ-EkCaTbpa22Wva0_v2Zm97xxX0QfKQMPnNPzOTf5K8xGiBc47f7_zYd6pZ7PdqWGAUF8ePklPMWJ7xnNPHD84nybMQdghRnOPiaXKSM0SYKPLT5Of5tWpGNTjfpd6mm-XlJlv5HxlJoRv6m3ep62yj2vZIqM6kHfxKhy30ag_j4HSIRLodW9WlzdjV6eBCGCHV0DThefLEqibAi2k_S75_PP-2-pxdfP20Xi0vMs0xGTJLCRiOOcUVUENEhUpuuUAVIYUSBhOgJeOWGgSc6xIYRZQioyxwAyi2cZa8PuruGx_kNJggCS8IFiW7JdZHwni1k_vetaq_kV45eRvwfS1VH7tpQFZCIMFwxVFeUsa4stZoUZgSW8ULg6LWh-m1sWrB6MOgVDMTnd90bitrfy1LLjDlPAq8mQR6fzVCGP5R8kTVKlYVv8FHMd26oOWyiEKYijyP1OIvVFwGWqd9B9bF-Czh7SwhMgP8Hmo1hiDXm8v_YL_MWXpkde9D6MHeDwQjeTDsXZPyYFg5GTamvXo4zPukO4fmfwD5KeW6</recordid><startdate>20220113</startdate><enddate>20220113</enddate><creator>Grau-Expósito, Judith</creator><creator>Perea, David</creator><creator>Suppi, Marina</creator><creator>Massana, Núria</creator><creator>Vergara, Ander</creator><creator>Soler, Maria José</creator><creator>Trinite, Benjamin</creator><creator>Blanco, Julià</creator><creator>García-Pérez, Javier</creator><creator>Alcamí, José</creator><creator>Serrano-Mollar, Anna</creator><creator>Rosado, Joel</creator><creator>Falcó, Vicenç</creator><creator>Genescà, Meritxell</creator><creator>Buzon, Maria J</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>ISN</scope><scope>ISR</scope><scope>3V.</scope><scope>7QL</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>COVID</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-4427-9413</orcidid></search><sort><creationdate>20220113</creationdate><title>Evaluation of SARS-CoV-2 entry, inflammation and new therapeutics in human lung tissue cells</title><author>Grau-Expósito, Judith ; Perea, David ; Suppi, Marina ; Massana, Núria ; Vergara, Ander ; Soler, Maria José ; Trinite, Benjamin ; Blanco, Julià ; García-Pérez, Javier ; Alcamí, José ; Serrano-Mollar, Anna ; Rosado, Joel ; Falcó, Vicenç ; Genescà, Meritxell ; Buzon, Maria J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c712t-f42ed71741be4d29b087f790b226a9d12e4857f4d0e77c8e540440dafe7de0963</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>ACE2</topic><topic>Adult</topic><topic>Alveoli</topic><topic>Analysis</topic><topic>Angiotensin-converting enzyme 2</topic><topic>Animals</topic><topic>Anti-inflammatory agents</topic><topic>Antiviral activity</topic><topic>Antiviral agents</topic><topic>Antiviral Agents - pharmacology</topic><topic>Antiviral Agents - therapeutic use</topic><topic>Axl protein</topic><topic>Biology and life sciences</topic><topic>CD147 antigen</topic><topic>Cell culture</topic><topic>Cell differentiation</topic><topic>Cell suspensions</topic><topic>Cells, Cultured</topic><topic>Chlorocebus aethiops</topic><topic>Coronaviruses</topic><topic>COVID-19</topic><topic>COVID-19 - immunology</topic><topic>COVID-19 - pathology</topic><topic>COVID-19 Drug Treatment</topic><topic>Dendritic cells</topic><topic>Dosage and administration</topic><topic>Drug development</topic><topic>Drug Evaluation, Preclinical</topic><topic>Drug resistance</topic><topic>Drugs, Investigational - pharmacology</topic><topic>Drugs, Investigational - therapeutic use</topic><topic>Gene expression</topic><topic>HEK293 Cells</topic><topic>Host-pathogen interactions</topic><topic>Host-Pathogen Interactions - drug effects</topic><topic>Host-virus relationships</topic><topic>Humans</topic><topic>Infection control</topic><topic>Infections</topic><topic>Inflammation</topic><topic>Inflammation - pathology</topic><topic>Inflammation - therapy</topic><topic>Inflammation - virology</topic><topic>Lung - pathology</topic><topic>Lung - virology</topic><topic>Lungs</topic><topic>Medicine and health sciences</topic><topic>Methods</topic><topic>Neutrophils</topic><topic>Nonsteroidal anti-inflammatory drugs</topic><topic>Phosphatase</topic><topic>Physiology</topic><topic>Proteins</topic><topic>Pulmonary function tests</topic><topic>Research and Analysis Methods</topic><topic>SARS-CoV-2 - drug effects</topic><topic>SARS-CoV-2 - physiology</topic><topic>Severe acute respiratory syndrome coronavirus 2</topic><topic>Thoracic surgery</topic><topic>Vero Cells</topic><topic>Viral diseases</topic><topic>Viral infections</topic><topic>Virus Internalization - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Grau-Expósito, Judith</creatorcontrib><creatorcontrib>Perea, David</creatorcontrib><creatorcontrib>Suppi, Marina</creatorcontrib><creatorcontrib>Massana, Núria</creatorcontrib><creatorcontrib>Vergara, Ander</creatorcontrib><creatorcontrib>Soler, Maria José</creatorcontrib><creatorcontrib>Trinite, Benjamin</creatorcontrib><creatorcontrib>Blanco, Julià</creatorcontrib><creatorcontrib>García-Pérez, Javier</creatorcontrib><creatorcontrib>Alcamí, José</creatorcontrib><creatorcontrib>Serrano-Mollar, Anna</creatorcontrib><creatorcontrib>Rosado, Joel</creatorcontrib><creatorcontrib>Falcó, Vicenç</creatorcontrib><creatorcontrib>Genescà, Meritxell</creatorcontrib><creatorcontrib>Buzon, Maria J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Canada</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>Coronavirus Research Database</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS pathogens</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Grau-Expósito, Judith</au><au>Perea, David</au><au>Suppi, Marina</au><au>Massana, Núria</au><au>Vergara, Ander</au><au>Soler, Maria José</au><au>Trinite, Benjamin</au><au>Blanco, Julià</au><au>García-Pérez, Javier</au><au>Alcamí, José</au><au>Serrano-Mollar, Anna</au><au>Rosado, Joel</au><au>Falcó, Vicenç</au><au>Genescà, Meritxell</au><au>Buzon, Maria J</au><au>Channappanavar, Rudra</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evaluation of SARS-CoV-2 entry, inflammation and new therapeutics in human lung tissue cells</atitle><jtitle>PLoS pathogens</jtitle><addtitle>PLoS Pathog</addtitle><date>2022-01-13</date><risdate>2022</risdate><volume>18</volume><issue>1</issue><spage>e1010171</spage><pages>e1010171-</pages><issn>1553-7374</issn><issn>1553-7366</issn><eissn>1553-7374</eissn><abstract>The development of physiological models that reproduce SARS-CoV-2 infection in primary human cells will be instrumental to identify host-pathogen interactions and potential therapeutics. Here, using cell suspensions directly from primary human lung tissues (HLT), we have developed a rapid platform for the identification of viral targets and the expression of viral entry factors, as well as for the screening of viral entry inhibitors and anti-inflammatory compounds. The direct use of HLT cells, without long-term cell culture and in vitro differentiation approaches, preserves main immune and structural cell populations, including the most susceptible cell targets for SARS-CoV-2; alveolar type II (AT-II) cells, while maintaining the expression of proteins involved in viral infection, such as ACE2, TMPRSS2, CD147 and AXL. Further, antiviral testing of 39 drug candidates reveals a highly reproducible method, suitable for different SARS-CoV-2 variants, and provides the identification of new compounds missed by conventional systems, such as VeroE6. Using this method, we also show that interferons do not modulate ACE2 expression, and that stimulation of local inflammatory responses can be modulated by different compounds with antiviral activity. Overall, we present a relevant and rapid method for the study of SARS-CoV-2.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>35025963</pmid><doi>10.1371/journal.ppat.1010171</doi><tpages>e1010171</tpages><orcidid>https://orcid.org/0000-0003-4427-9413</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1553-7374 |
| ispartof | PLoS pathogens, 2022-01, Vol.18 (1), p.e1010171 |
| issn | 1553-7374 1553-7366 1553-7374 |
| language | eng |
| recordid | cdi_plos_journals_2762198596 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; PubMed Central Open Access; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | ACE2 Adult Alveoli Analysis Angiotensin-converting enzyme 2 Animals Anti-inflammatory agents Antiviral activity Antiviral agents Antiviral Agents - pharmacology Antiviral Agents - therapeutic use Axl protein Biology and life sciences CD147 antigen Cell culture Cell differentiation Cell suspensions Cells, Cultured Chlorocebus aethiops Coronaviruses COVID-19 COVID-19 - immunology COVID-19 - pathology COVID-19 Drug Treatment Dendritic cells Dosage and administration Drug development Drug Evaluation, Preclinical Drug resistance Drugs, Investigational - pharmacology Drugs, Investigational - therapeutic use Gene expression HEK293 Cells Host-pathogen interactions Host-Pathogen Interactions - drug effects Host-virus relationships Humans Infection control Infections Inflammation Inflammation - pathology Inflammation - therapy Inflammation - virology Lung - pathology Lung - virology Lungs Medicine and health sciences Methods Neutrophils Nonsteroidal anti-inflammatory drugs Phosphatase Physiology Proteins Pulmonary function tests Research and Analysis Methods SARS-CoV-2 - drug effects SARS-CoV-2 - physiology Severe acute respiratory syndrome coronavirus 2 Thoracic surgery Vero Cells Viral diseases Viral infections Virus Internalization - drug effects |
| title | Evaluation of SARS-CoV-2 entry, inflammation and new therapeutics in human lung tissue cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-22T06%3A10%3A33IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Evaluation%20of%20SARS-CoV-2%20entry,%20inflammation%20and%20new%20therapeutics%20in%20human%20lung%20tissue%20cells&rft.jtitle=PLoS%20pathogens&rft.au=Grau-Exp%C3%B3sito,%20Judith&rft.date=2022-01-13&rft.volume=18&rft.issue=1&rft.spage=e1010171&rft.pages=e1010171-&rft.issn=1553-7374&rft.eissn=1553-7374&rft_id=info:doi/10.1371/journal.ppat.1010171&rft_dat=%3Cgale_plos_%3EA691414933%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2762198596&rft_id=info:pmid/35025963&rft_galeid=A691414933&rft_doaj_id=oai_doaj_org_article_b990951b70384557affdc96d81fa76d0&rfr_iscdi=true |