Abortive infection of bat fibroblasts with SARS-CoV-2
Bats are tolerant to highly pathogenic viruses such as Marburg, Ebola, and Nipah, suggesting the presence of a unique immune tolerance toward viral infection. Here, we compared severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of human and bat ( ) pluripotent cells and fibroblas...
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creator | Bisht, Punam Gallagher, Michael D Barrasa, M Inmaculada Boucau, Julie Harding, Alfred Déjosez, Marion Godoy-Parejo, Carlos Bisher, Margaret E de Nola, Giovanni Lytton-Jean, Abigail K R Gehrke, Lee Zwaka, Thomas P Jaenisch, Rudolf |
description | Bats are tolerant to highly pathogenic viruses such as Marburg, Ebola, and Nipah, suggesting the presence of a unique immune tolerance toward viral infection. Here, we compared severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of human and bat (
) pluripotent cells and fibroblasts. Since bat cells do not express an angiotensin-converting enzyme 2 (ACE2) receptor that allows virus infection, we transduced the human ACE2 (hA) receptor into the cells and found that transduced cells can be infected with SARS-CoV-2. Compared to human embryonic stem cells-hA, infected bat induced Pluripotent Stem Cells (iPSCs)-hA produced about a 100-fold lower level of infectious virus and displayed lower toxicity. In contrast, bat embryonic fibroblast-hA produced no infectious virus while being infectable and synthesizing viral RNA and proteins, suggesting abortive infection. Indeed, electron microscopy failed to detect virus-like particles in infected bat fibroblasts in contrast to bat iPSCs or human cells, consistent with the latter producing infectious viruses. This suggests that bat somatic but not pluripotent cells have an effective mechanism to control virus replication. Consistent with previous results by others, we find that bat cells have a constitutively activated innate immune system, which might limit SARS-CoV-2 infection compared to human cells. |
doi_str_mv | 10.1073/pnas.2406773121 |
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) pluripotent cells and fibroblasts. Since bat cells do not express an angiotensin-converting enzyme 2 (ACE2) receptor that allows virus infection, we transduced the human ACE2 (hA) receptor into the cells and found that transduced cells can be infected with SARS-CoV-2. Compared to human embryonic stem cells-hA, infected bat induced Pluripotent Stem Cells (iPSCs)-hA produced about a 100-fold lower level of infectious virus and displayed lower toxicity. In contrast, bat embryonic fibroblast-hA produced no infectious virus while being infectable and synthesizing viral RNA and proteins, suggesting abortive infection. Indeed, electron microscopy failed to detect virus-like particles in infected bat fibroblasts in contrast to bat iPSCs or human cells, consistent with the latter producing infectious viruses. This suggests that bat somatic but not pluripotent cells have an effective mechanism to control virus replication. Consistent with previous results by others, we find that bat cells have a constitutively activated innate immune system, which might limit SARS-CoV-2 infection compared to human cells.</description><identifier>ISSN: 0027-8424</identifier><identifier>ISSN: 1091-6490</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.2406773121</identifier><identifier>PMID: 39401365</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>ACE2 ; Angiotensin ; Angiotensin-converting enzyme 2 ; Angiotensin-Converting Enzyme 2 - genetics ; Angiotensin-Converting Enzyme 2 - metabolism ; Animals ; Biological Sciences ; Chiroptera - virology ; Coronaviruses ; COVID-19 ; COVID-19 - immunology ; COVID-19 - virology ; Electron microscopy ; Embryo cells ; Embryo fibroblasts ; Fibroblasts ; Fibroblasts - metabolism ; Fibroblasts - virology ; Humans ; Immune system ; Immunological tolerance ; Induced Pluripotent Stem Cells - metabolism ; Induced Pluripotent Stem Cells - virology ; Infections ; Innate immunity ; Peptidyl-dipeptidase A ; Pluripotency ; Receptors ; Respiratory diseases ; Rhinolophus ferrumequinum ; RNA viruses ; SARS-CoV-2 - immunology ; SARS-CoV-2 - physiology ; Severe acute respiratory syndrome coronavirus 2 ; Stem cells ; Toxicity ; Viral diseases ; Viral infections ; Virus Replication ; Virus-like particles ; Viruses</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2024-10, Vol.121 (43), p.e2406773121</ispartof><rights>Copyright National Academy of Sciences Oct 22, 2024</rights><rights>Copyright © 2024 the Author(s). Published by PNAS. 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c306t-73c416b8ea6a8b171fd00480129035e76cb8acf78eb3261c1c354e72008ab87e3</cites><orcidid>0000-0003-3393-4814 ; 0000-0001-6731-7238 ; 0000-0002-9387-8212 ; 0000-0002-2109-1293</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39401365$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bisht, Punam</creatorcontrib><creatorcontrib>Gallagher, Michael D</creatorcontrib><creatorcontrib>Barrasa, M Inmaculada</creatorcontrib><creatorcontrib>Boucau, Julie</creatorcontrib><creatorcontrib>Harding, Alfred</creatorcontrib><creatorcontrib>Déjosez, Marion</creatorcontrib><creatorcontrib>Godoy-Parejo, Carlos</creatorcontrib><creatorcontrib>Bisher, Margaret E</creatorcontrib><creatorcontrib>de Nola, Giovanni</creatorcontrib><creatorcontrib>Lytton-Jean, Abigail K R</creatorcontrib><creatorcontrib>Gehrke, Lee</creatorcontrib><creatorcontrib>Zwaka, Thomas P</creatorcontrib><creatorcontrib>Jaenisch, Rudolf</creatorcontrib><title>Abortive infection of bat fibroblasts with SARS-CoV-2</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Bats are tolerant to highly pathogenic viruses such as Marburg, Ebola, and Nipah, suggesting the presence of a unique immune tolerance toward viral infection. Here, we compared severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of human and bat (
) pluripotent cells and fibroblasts. Since bat cells do not express an angiotensin-converting enzyme 2 (ACE2) receptor that allows virus infection, we transduced the human ACE2 (hA) receptor into the cells and found that transduced cells can be infected with SARS-CoV-2. Compared to human embryonic stem cells-hA, infected bat induced Pluripotent Stem Cells (iPSCs)-hA produced about a 100-fold lower level of infectious virus and displayed lower toxicity. In contrast, bat embryonic fibroblast-hA produced no infectious virus while being infectable and synthesizing viral RNA and proteins, suggesting abortive infection. Indeed, electron microscopy failed to detect virus-like particles in infected bat fibroblasts in contrast to bat iPSCs or human cells, consistent with the latter producing infectious viruses. This suggests that bat somatic but not pluripotent cells have an effective mechanism to control virus replication. Consistent with previous results by others, we find that bat cells have a constitutively activated innate immune system, which might limit SARS-CoV-2 infection compared to human cells.</description><subject>ACE2</subject><subject>Angiotensin</subject><subject>Angiotensin-converting enzyme 2</subject><subject>Angiotensin-Converting Enzyme 2 - genetics</subject><subject>Angiotensin-Converting Enzyme 2 - metabolism</subject><subject>Animals</subject><subject>Biological Sciences</subject><subject>Chiroptera - virology</subject><subject>Coronaviruses</subject><subject>COVID-19</subject><subject>COVID-19 - immunology</subject><subject>COVID-19 - virology</subject><subject>Electron microscopy</subject><subject>Embryo cells</subject><subject>Embryo fibroblasts</subject><subject>Fibroblasts</subject><subject>Fibroblasts - metabolism</subject><subject>Fibroblasts - virology</subject><subject>Humans</subject><subject>Immune system</subject><subject>Immunological tolerance</subject><subject>Induced Pluripotent Stem Cells - metabolism</subject><subject>Induced Pluripotent Stem Cells - virology</subject><subject>Infections</subject><subject>Innate immunity</subject><subject>Peptidyl-dipeptidase A</subject><subject>Pluripotency</subject><subject>Receptors</subject><subject>Respiratory diseases</subject><subject>Rhinolophus ferrumequinum</subject><subject>RNA viruses</subject><subject>SARS-CoV-2 - immunology</subject><subject>SARS-CoV-2 - physiology</subject><subject>Severe acute respiratory syndrome coronavirus 2</subject><subject>Stem cells</subject><subject>Toxicity</subject><subject>Viral diseases</subject><subject>Viral infections</subject><subject>Virus Replication</subject><subject>Virus-like particles</subject><subject>Viruses</subject><issn>0027-8424</issn><issn>1091-6490</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkctLxDAQh4Mouj7O3qTgxUvXmSRN0pMsiy8QBF_XkMRUI91mTbqK_70V1-dpDvPNj5n5CNlFGCNIdjjvTB5TDkJKhhRXyAihxlLwGlbJCIDKUnHKN8hmzk8AUFcK1skGqzkgE9WIVBMbUx9efBG6xrs-xK6ITWFNXzTBpmhbk_tcvIb-sbieXF2X03hX0m2y1pg2-51l3SK3J8c307Py4vL0fDq5KB0D0ZeSOY7CKm-EURYlNvcAXAHSGljlpXBWGddI5S2jAh06VnEvKYAyVknPtsjRZ-58YWf-3vmuT6bV8xRmJr3paIL-2-nCo36ILxqxQlZXfEg4WCak-LzwudezkJ1vW9P5uMiaIQohh6_IAd3_hz7FReqG-waKUlEzgWKgDj8pl2LOyTff2yDoDyf6w4n-cTJM7P0-4pv_ksDeAZ09hfA</recordid><startdate>20241022</startdate><enddate>20241022</enddate><creator>Bisht, Punam</creator><creator>Gallagher, Michael D</creator><creator>Barrasa, M Inmaculada</creator><creator>Boucau, Julie</creator><creator>Harding, Alfred</creator><creator>Déjosez, Marion</creator><creator>Godoy-Parejo, Carlos</creator><creator>Bisher, Margaret E</creator><creator>de Nola, Giovanni</creator><creator>Lytton-Jean, Abigail K R</creator><creator>Gehrke, Lee</creator><creator>Zwaka, Thomas P</creator><creator>Jaenisch, Rudolf</creator><general>National Academy of Sciences</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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-3393-4814</orcidid><orcidid>https://orcid.org/0000-0001-6731-7238</orcidid><orcidid>https://orcid.org/0000-0002-9387-8212</orcidid><orcidid>https://orcid.org/0000-0002-2109-1293</orcidid></search><sort><creationdate>20241022</creationdate><title>Abortive infection of bat fibroblasts with SARS-CoV-2</title><author>Bisht, Punam ; Gallagher, Michael D ; Barrasa, M Inmaculada ; Boucau, Julie ; Harding, Alfred ; Déjosez, Marion ; Godoy-Parejo, Carlos ; Bisher, Margaret E ; de Nola, Giovanni ; Lytton-Jean, Abigail K R ; Gehrke, Lee ; Zwaka, Thomas P ; Jaenisch, Rudolf</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c306t-73c416b8ea6a8b171fd00480129035e76cb8acf78eb3261c1c354e72008ab87e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>ACE2</topic><topic>Angiotensin</topic><topic>Angiotensin-converting enzyme 2</topic><topic>Angiotensin-Converting Enzyme 2 - 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Here, we compared severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of human and bat (
) pluripotent cells and fibroblasts. Since bat cells do not express an angiotensin-converting enzyme 2 (ACE2) receptor that allows virus infection, we transduced the human ACE2 (hA) receptor into the cells and found that transduced cells can be infected with SARS-CoV-2. Compared to human embryonic stem cells-hA, infected bat induced Pluripotent Stem Cells (iPSCs)-hA produced about a 100-fold lower level of infectious virus and displayed lower toxicity. In contrast, bat embryonic fibroblast-hA produced no infectious virus while being infectable and synthesizing viral RNA and proteins, suggesting abortive infection. Indeed, electron microscopy failed to detect virus-like particles in infected bat fibroblasts in contrast to bat iPSCs or human cells, consistent with the latter producing infectious viruses. This suggests that bat somatic but not pluripotent cells have an effective mechanism to control virus replication. Consistent with previous results by others, we find that bat cells have a constitutively activated innate immune system, which might limit SARS-CoV-2 infection compared to human cells.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>39401365</pmid><doi>10.1073/pnas.2406773121</doi><orcidid>https://orcid.org/0000-0003-3393-4814</orcidid><orcidid>https://orcid.org/0000-0001-6731-7238</orcidid><orcidid>https://orcid.org/0000-0002-9387-8212</orcidid><orcidid>https://orcid.org/0000-0002-2109-1293</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | ACE2 Angiotensin Angiotensin-converting enzyme 2 Angiotensin-Converting Enzyme 2 - genetics Angiotensin-Converting Enzyme 2 - metabolism Animals Biological Sciences Chiroptera - virology Coronaviruses COVID-19 COVID-19 - immunology COVID-19 - virology Electron microscopy Embryo cells Embryo fibroblasts Fibroblasts Fibroblasts - metabolism Fibroblasts - virology Humans Immune system Immunological tolerance Induced Pluripotent Stem Cells - metabolism Induced Pluripotent Stem Cells - virology Infections Innate immunity Peptidyl-dipeptidase A Pluripotency Receptors Respiratory diseases Rhinolophus ferrumequinum RNA viruses SARS-CoV-2 - immunology SARS-CoV-2 - physiology Severe acute respiratory syndrome coronavirus 2 Stem cells Toxicity Viral diseases Viral infections Virus Replication Virus-like particles Viruses |
title | Abortive infection of bat fibroblasts with SARS-CoV-2 |
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