CD169-mediated restrictive SARS-CoV-2 infection of macrophages induces pro-inflammatory responses
Exacerbated and persistent innate immune response marked by pro-inflammatory cytokine expression is thought to be a major driver of chronic COVID-19 pathology. Although macrophages are not the primary target cells of SARS-CoV-2 infection in humans, viral RNA and antigens in activated monocytes and m...
Gespeichert in:
| Veröffentlicht in: | PLoS pathogens 2022-10, Vol.18 (10), p.e1010479 |
|---|---|
| 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 | 10 |
| container_start_page | e1010479 |
| container_title | PLoS pathogens |
| container_volume | 18 |
| creator | Jalloh, Sallieu Olejnik, Judith Berrigan, Jacob Nisa, Annuurun Suder, Ellen L Akiyama, Hisashi Lei, Maohua Ramaswamy, Sita Tyagi, Sanjay Bushkin, Yuri Mühlberger, Elke Gummuluru, Suryaram |
| description | Exacerbated and persistent innate immune response marked by pro-inflammatory cytokine expression is thought to be a major driver of chronic COVID-19 pathology. Although macrophages are not the primary target cells of SARS-CoV-2 infection in humans, viral RNA and antigens in activated monocytes and macrophages have been detected in post-mortem samples, and dysfunctional monocytes and macrophages have been hypothesized to contribute to a protracted hyper-inflammatory state in COVID-19 patients. In this study, we demonstrate that CD169, a myeloid cell specific I-type lectin, facilitated ACE2-independent SARS-CoV-2 fusion and entry in macrophages. CD169-mediated SARS-CoV-2 entry in macrophages resulted in expression of viral genomic and subgenomic RNAs with minimal viral protein expression and no infectious viral particle release, suggesting a post-entry restriction of the SARS-CoV-2 replication cycle. Intriguingly this post-entry replication block was alleviated by exogenous ACE2 expression in macrophages. Restricted expression of viral genomic and subgenomic RNA in CD169+ macrophages elicited a pro-inflammatory cytokine expression (TNFα, IL-6 and IL-1β) in a RIG-I, MDA-5 and MAVS-dependent manner, which was suppressed by remdesivir treatment. These findings suggest that de novo expression of SARS-CoV-2 RNA in macrophages contributes to the pro-inflammatory cytokine signature and that blocking CD169-mediated ACE2 independent infection and subsequent activation of macrophages by viral RNA might alleviate COVID-19-associated hyperinflammatory response. |
| doi_str_mv | 10.1371/journal.ppat.1010479 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_2737136207</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A724759404</galeid><doaj_id>oai_doaj_org_article_85f8d9b4a0a64408996252c3e4b0c0a8</doaj_id><sourcerecordid>A724759404</sourcerecordid><originalsourceid>FETCH-LOGICAL-c591t-bebc94a4530682234684b1879f353f36773d0fc94e6267c42f3d0c19ef5ea0a23</originalsourceid><addsrcrecordid>eNqVkktv1DAUhSMEoqXwDxCMxAYWGfyKHW-QRsNrpAqkDrC1HMeeepTEqZ1U9N9zw6RVB3WDIsXJ9XePc09Olr3EaImpwO_3YYydbpZ9r4clRhgxIR9lp7goaC6oYI_vPZ9kz1LaI8QwxfxpdkI5EZKUxWmm1x8xl3lra68HWy-iTUP0ZvDXdrFdXWzzdfiVk4XvnIVi6BbBLVptYugv9c4m2KhHA2sfQw5Qo9tWDyHeTEJ96JJNz7MnTjfJvpjXs-zn508_1l_z8-9fNuvVeW4KiYe8spWRTLOCIl4SQhkvWYVLIR0tqKNcCFojB4jlhAvDiIN3g6V1hdVIE3qWvT7o9k1IanYnKQLzY5gXCSA2B6IOeq_66Fsdb1TQXv0thLhTOg7eNFaVhStrWTFQ5oyhUkpOCmKoZRUySJeg9WE-bazAPGO7IermSPR4p_OXaheuleSUSCxB4O0sEMPVCK6r1idjm0Z3NozTd5MSM7hxQN_8gz483UztNAwA_yLAuWYSVStBmCgkQwyo5QMUXLVtvQmddR7qRw3vjhqAGezvYafHlNRme_Ef7Ldjlh1YyFJK0bo77zBSU8Bvh1RTwNUccGh7dd_3u6bbRNM_5cz0-g</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2737136207</pqid></control><display><type>article</type><title>CD169-mediated restrictive SARS-CoV-2 infection of macrophages induces pro-inflammatory responses</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>PubMed Central Open Access</source><source>Public Library of Science (PLoS)</source><creator>Jalloh, Sallieu ; Olejnik, Judith ; Berrigan, Jacob ; Nisa, Annuurun ; Suder, Ellen L ; Akiyama, Hisashi ; Lei, Maohua ; Ramaswamy, Sita ; Tyagi, Sanjay ; Bushkin, Yuri ; Mühlberger, Elke ; Gummuluru, Suryaram</creator><creatorcontrib>Jalloh, Sallieu ; Olejnik, Judith ; Berrigan, Jacob ; Nisa, Annuurun ; Suder, Ellen L ; Akiyama, Hisashi ; Lei, Maohua ; Ramaswamy, Sita ; Tyagi, Sanjay ; Bushkin, Yuri ; Mühlberger, Elke ; Gummuluru, Suryaram</creatorcontrib><description>Exacerbated and persistent innate immune response marked by pro-inflammatory cytokine expression is thought to be a major driver of chronic COVID-19 pathology. Although macrophages are not the primary target cells of SARS-CoV-2 infection in humans, viral RNA and antigens in activated monocytes and macrophages have been detected in post-mortem samples, and dysfunctional monocytes and macrophages have been hypothesized to contribute to a protracted hyper-inflammatory state in COVID-19 patients. In this study, we demonstrate that CD169, a myeloid cell specific I-type lectin, facilitated ACE2-independent SARS-CoV-2 fusion and entry in macrophages. CD169-mediated SARS-CoV-2 entry in macrophages resulted in expression of viral genomic and subgenomic RNAs with minimal viral protein expression and no infectious viral particle release, suggesting a post-entry restriction of the SARS-CoV-2 replication cycle. Intriguingly this post-entry replication block was alleviated by exogenous ACE2 expression in macrophages. Restricted expression of viral genomic and subgenomic RNA in CD169+ macrophages elicited a pro-inflammatory cytokine expression (TNFα, IL-6 and IL-1β) in a RIG-I, MDA-5 and MAVS-dependent manner, which was suppressed by remdesivir treatment. These findings suggest that de novo expression of SARS-CoV-2 RNA in macrophages contributes to the pro-inflammatory cytokine signature and that blocking CD169-mediated ACE2 independent infection and subsequent activation of macrophages by viral RNA might alleviate COVID-19-associated hyperinflammatory response.</description><identifier>ISSN: 1553-7374</identifier><identifier>ISSN: 1553-7366</identifier><identifier>EISSN: 1553-7374</identifier><identifier>DOI: 10.1371/journal.ppat.1010479</identifier><identifier>PMID: 36279285</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>ACE2 ; Angiotensin-converting enzyme 2 ; Angiotensin-Converting Enzyme 2 - genetics ; Antigens ; Blocking ; Cell activation ; Coronaviruses ; COVID-19 ; Cytokines ; Cytokines - metabolism ; Flow cytometry ; Gene expression ; Genomes ; Genomics ; Humans ; IL-1β ; Immune response ; Infections ; Inflammation ; Innate immunity ; Interleukin 6 ; Long COVID ; Macrophages ; Monocytes ; Physiological aspects ; Proteins ; Replication ; Ribonucleic acid ; RNA ; RNA, Viral - metabolism ; SARS-CoV-2 ; Severe acute respiratory syndrome coronavirus 2 ; Tumor necrosis factor-α ; Viral diseases ; Viral infections</subject><ispartof>PLoS pathogens, 2022-10, Vol.18 (10), p.e1010479</ispartof><rights>COPYRIGHT 2022 Public Library of Science</rights><rights>2022 Jalloh 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 Jalloh et al 2022 Jalloh et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c591t-bebc94a4530682234684b1879f353f36773d0fc94e6267c42f3d0c19ef5ea0a23</citedby><cites>FETCH-LOGICAL-c591t-bebc94a4530682234684b1879f353f36773d0fc94e6267c42f3d0c19ef5ea0a23</cites><orcidid>0000-0002-8606-8481</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/PMC9632919/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9632919/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36279285$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jalloh, Sallieu</creatorcontrib><creatorcontrib>Olejnik, Judith</creatorcontrib><creatorcontrib>Berrigan, Jacob</creatorcontrib><creatorcontrib>Nisa, Annuurun</creatorcontrib><creatorcontrib>Suder, Ellen L</creatorcontrib><creatorcontrib>Akiyama, Hisashi</creatorcontrib><creatorcontrib>Lei, Maohua</creatorcontrib><creatorcontrib>Ramaswamy, Sita</creatorcontrib><creatorcontrib>Tyagi, Sanjay</creatorcontrib><creatorcontrib>Bushkin, Yuri</creatorcontrib><creatorcontrib>Mühlberger, Elke</creatorcontrib><creatorcontrib>Gummuluru, Suryaram</creatorcontrib><title>CD169-mediated restrictive SARS-CoV-2 infection of macrophages induces pro-inflammatory responses</title><title>PLoS pathogens</title><addtitle>PLoS Pathog</addtitle><description>Exacerbated and persistent innate immune response marked by pro-inflammatory cytokine expression is thought to be a major driver of chronic COVID-19 pathology. Although macrophages are not the primary target cells of SARS-CoV-2 infection in humans, viral RNA and antigens in activated monocytes and macrophages have been detected in post-mortem samples, and dysfunctional monocytes and macrophages have been hypothesized to contribute to a protracted hyper-inflammatory state in COVID-19 patients. In this study, we demonstrate that CD169, a myeloid cell specific I-type lectin, facilitated ACE2-independent SARS-CoV-2 fusion and entry in macrophages. CD169-mediated SARS-CoV-2 entry in macrophages resulted in expression of viral genomic and subgenomic RNAs with minimal viral protein expression and no infectious viral particle release, suggesting a post-entry restriction of the SARS-CoV-2 replication cycle. Intriguingly this post-entry replication block was alleviated by exogenous ACE2 expression in macrophages. Restricted expression of viral genomic and subgenomic RNA in CD169+ macrophages elicited a pro-inflammatory cytokine expression (TNFα, IL-6 and IL-1β) in a RIG-I, MDA-5 and MAVS-dependent manner, which was suppressed by remdesivir treatment. These findings suggest that de novo expression of SARS-CoV-2 RNA in macrophages contributes to the pro-inflammatory cytokine signature and that blocking CD169-mediated ACE2 independent infection and subsequent activation of macrophages by viral RNA might alleviate COVID-19-associated hyperinflammatory response.</description><subject>ACE2</subject><subject>Angiotensin-converting enzyme 2</subject><subject>Angiotensin-Converting Enzyme 2 - genetics</subject><subject>Antigens</subject><subject>Blocking</subject><subject>Cell activation</subject><subject>Coronaviruses</subject><subject>COVID-19</subject><subject>Cytokines</subject><subject>Cytokines - metabolism</subject><subject>Flow cytometry</subject><subject>Gene expression</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Humans</subject><subject>IL-1β</subject><subject>Immune response</subject><subject>Infections</subject><subject>Inflammation</subject><subject>Innate immunity</subject><subject>Interleukin 6</subject><subject>Long COVID</subject><subject>Macrophages</subject><subject>Monocytes</subject><subject>Physiological aspects</subject><subject>Proteins</subject><subject>Replication</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA, Viral - metabolism</subject><subject>SARS-CoV-2</subject><subject>Severe acute respiratory syndrome coronavirus 2</subject><subject>Tumor necrosis factor-α</subject><subject>Viral diseases</subject><subject>Viral infections</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>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqVkktv1DAUhSMEoqXwDxCMxAYWGfyKHW-QRsNrpAqkDrC1HMeeepTEqZ1U9N9zw6RVB3WDIsXJ9XePc09Olr3EaImpwO_3YYydbpZ9r4clRhgxIR9lp7goaC6oYI_vPZ9kz1LaI8QwxfxpdkI5EZKUxWmm1x8xl3lra68HWy-iTUP0ZvDXdrFdXWzzdfiVk4XvnIVi6BbBLVptYugv9c4m2KhHA2sfQw5Qo9tWDyHeTEJ96JJNz7MnTjfJvpjXs-zn508_1l_z8-9fNuvVeW4KiYe8spWRTLOCIl4SQhkvWYVLIR0tqKNcCFojB4jlhAvDiIN3g6V1hdVIE3qWvT7o9k1IanYnKQLzY5gXCSA2B6IOeq_66Fsdb1TQXv0thLhTOg7eNFaVhStrWTFQ5oyhUkpOCmKoZRUySJeg9WE-bazAPGO7IermSPR4p_OXaheuleSUSCxB4O0sEMPVCK6r1idjm0Z3NozTd5MSM7hxQN_8gz483UztNAwA_yLAuWYSVStBmCgkQwyo5QMUXLVtvQmddR7qRw3vjhqAGezvYafHlNRme_Ef7Ldjlh1YyFJK0bo77zBSU8Bvh1RTwNUccGh7dd_3u6bbRNM_5cz0-g</recordid><startdate>20221024</startdate><enddate>20221024</enddate><creator>Jalloh, Sallieu</creator><creator>Olejnik, Judith</creator><creator>Berrigan, Jacob</creator><creator>Nisa, Annuurun</creator><creator>Suder, Ellen L</creator><creator>Akiyama, Hisashi</creator><creator>Lei, Maohua</creator><creator>Ramaswamy, Sita</creator><creator>Tyagi, Sanjay</creator><creator>Bushkin, Yuri</creator><creator>Mühlberger, Elke</creator><creator>Gummuluru, Suryaram</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>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-8606-8481</orcidid></search><sort><creationdate>20221024</creationdate><title>CD169-mediated restrictive SARS-CoV-2 infection of macrophages induces pro-inflammatory responses</title><author>Jalloh, Sallieu ; Olejnik, Judith ; Berrigan, Jacob ; Nisa, Annuurun ; Suder, Ellen L ; Akiyama, Hisashi ; Lei, Maohua ; Ramaswamy, Sita ; Tyagi, Sanjay ; Bushkin, Yuri ; Mühlberger, Elke ; Gummuluru, Suryaram</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c591t-bebc94a4530682234684b1879f353f36773d0fc94e6267c42f3d0c19ef5ea0a23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>ACE2</topic><topic>Angiotensin-converting enzyme 2</topic><topic>Angiotensin-Converting Enzyme 2 - genetics</topic><topic>Antigens</topic><topic>Blocking</topic><topic>Cell activation</topic><topic>Coronaviruses</topic><topic>COVID-19</topic><topic>Cytokines</topic><topic>Cytokines - metabolism</topic><topic>Flow cytometry</topic><topic>Gene expression</topic><topic>Genomes</topic><topic>Genomics</topic><topic>Humans</topic><topic>IL-1β</topic><topic>Immune response</topic><topic>Infections</topic><topic>Inflammation</topic><topic>Innate immunity</topic><topic>Interleukin 6</topic><topic>Long COVID</topic><topic>Macrophages</topic><topic>Monocytes</topic><topic>Physiological aspects</topic><topic>Proteins</topic><topic>Replication</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA, Viral - metabolism</topic><topic>SARS-CoV-2</topic><topic>Severe acute respiratory syndrome coronavirus 2</topic><topic>Tumor necrosis factor-α</topic><topic>Viral diseases</topic><topic>Viral infections</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jalloh, Sallieu</creatorcontrib><creatorcontrib>Olejnik, Judith</creatorcontrib><creatorcontrib>Berrigan, Jacob</creatorcontrib><creatorcontrib>Nisa, Annuurun</creatorcontrib><creatorcontrib>Suder, Ellen L</creatorcontrib><creatorcontrib>Akiyama, Hisashi</creatorcontrib><creatorcontrib>Lei, Maohua</creatorcontrib><creatorcontrib>Ramaswamy, Sita</creatorcontrib><creatorcontrib>Tyagi, Sanjay</creatorcontrib><creatorcontrib>Bushkin, Yuri</creatorcontrib><creatorcontrib>Mühlberger, Elke</creatorcontrib><creatorcontrib>Gummuluru, Suryaram</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>MEDLINE - Academic</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>Jalloh, Sallieu</au><au>Olejnik, Judith</au><au>Berrigan, Jacob</au><au>Nisa, Annuurun</au><au>Suder, Ellen L</au><au>Akiyama, Hisashi</au><au>Lei, Maohua</au><au>Ramaswamy, Sita</au><au>Tyagi, Sanjay</au><au>Bushkin, Yuri</au><au>Mühlberger, Elke</au><au>Gummuluru, Suryaram</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CD169-mediated restrictive SARS-CoV-2 infection of macrophages induces pro-inflammatory responses</atitle><jtitle>PLoS pathogens</jtitle><addtitle>PLoS Pathog</addtitle><date>2022-10-24</date><risdate>2022</risdate><volume>18</volume><issue>10</issue><spage>e1010479</spage><pages>e1010479-</pages><issn>1553-7374</issn><issn>1553-7366</issn><eissn>1553-7374</eissn><abstract>Exacerbated and persistent innate immune response marked by pro-inflammatory cytokine expression is thought to be a major driver of chronic COVID-19 pathology. Although macrophages are not the primary target cells of SARS-CoV-2 infection in humans, viral RNA and antigens in activated monocytes and macrophages have been detected in post-mortem samples, and dysfunctional monocytes and macrophages have been hypothesized to contribute to a protracted hyper-inflammatory state in COVID-19 patients. In this study, we demonstrate that CD169, a myeloid cell specific I-type lectin, facilitated ACE2-independent SARS-CoV-2 fusion and entry in macrophages. CD169-mediated SARS-CoV-2 entry in macrophages resulted in expression of viral genomic and subgenomic RNAs with minimal viral protein expression and no infectious viral particle release, suggesting a post-entry restriction of the SARS-CoV-2 replication cycle. Intriguingly this post-entry replication block was alleviated by exogenous ACE2 expression in macrophages. Restricted expression of viral genomic and subgenomic RNA in CD169+ macrophages elicited a pro-inflammatory cytokine expression (TNFα, IL-6 and IL-1β) in a RIG-I, MDA-5 and MAVS-dependent manner, which was suppressed by remdesivir treatment. These findings suggest that de novo expression of SARS-CoV-2 RNA in macrophages contributes to the pro-inflammatory cytokine signature and that blocking CD169-mediated ACE2 independent infection and subsequent activation of macrophages by viral RNA might alleviate COVID-19-associated hyperinflammatory response.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>36279285</pmid><doi>10.1371/journal.ppat.1010479</doi><tpages>e1010479</tpages><orcidid>https://orcid.org/0000-0002-8606-8481</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1553-7374 |
| ispartof | PLoS pathogens, 2022-10, Vol.18 (10), p.e1010479 |
| issn | 1553-7374 1553-7366 1553-7374 |
| language | eng |
| recordid | cdi_plos_journals_2737136207 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; PubMed Central Open Access; Public Library of Science (PLoS) |
| subjects | ACE2 Angiotensin-converting enzyme 2 Angiotensin-Converting Enzyme 2 - genetics Antigens Blocking Cell activation Coronaviruses COVID-19 Cytokines Cytokines - metabolism Flow cytometry Gene expression Genomes Genomics Humans IL-1β Immune response Infections Inflammation Innate immunity Interleukin 6 Long COVID Macrophages Monocytes Physiological aspects Proteins Replication Ribonucleic acid RNA RNA, Viral - metabolism SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 Tumor necrosis factor-α Viral diseases Viral infections |
| title | CD169-mediated restrictive SARS-CoV-2 infection of macrophages induces pro-inflammatory responses |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T17%3A44%3A06IST&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=CD169-mediated%20restrictive%20SARS-CoV-2%20infection%20of%20macrophages%20induces%20pro-inflammatory%20responses&rft.jtitle=PLoS%20pathogens&rft.au=Jalloh,%20Sallieu&rft.date=2022-10-24&rft.volume=18&rft.issue=10&rft.spage=e1010479&rft.pages=e1010479-&rft.issn=1553-7374&rft.eissn=1553-7374&rft_id=info:doi/10.1371/journal.ppat.1010479&rft_dat=%3Cgale_plos_%3EA724759404%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=2737136207&rft_id=info:pmid/36279285&rft_galeid=A724759404&rft_doaj_id=oai_doaj_org_article_85f8d9b4a0a64408996252c3e4b0c0a8&rfr_iscdi=true |