Human cytomegalovirus exploits STING signaling and counteracts IFN/ISG induction to facilitate infection of dendritic cells
Abstract Human cytomegalovirus (HCMV) is a widespread pathogen that in immunocompromised hosts can cause life-threatening disease. Studying HCMV-exposed monocyte-derived dendritic cells by single-cell RNA sequencing, we observe that most cells are entered by the virus, whereas less than 30% of them...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-45614-3 |
| _version_ | 1827326867819986944 |
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| author | Bibiana Costa Jennifer Becker Tobias Krammer Felix Mulenge Verónica Durán Andreas Pavlou Olivia Luise Gern Xiaojing Chu Yang Li Luka Čičin-Šain Britta Eiz-Vesper Martin Messerle Lars Dölken Antoine-Emmanuel Saliba Florian Erhard Ulrich Kalinke |
| author_facet | Bibiana Costa Jennifer Becker Tobias Krammer Felix Mulenge Verónica Durán Andreas Pavlou Olivia Luise Gern Xiaojing Chu Yang Li Luka Čičin-Šain Britta Eiz-Vesper Martin Messerle Lars Dölken Antoine-Emmanuel Saliba Florian Erhard Ulrich Kalinke |
| author_sort | Bibiana Costa |
| collection | DOAJ |
| description | Abstract Human cytomegalovirus (HCMV) is a widespread pathogen that in immunocompromised hosts can cause life-threatening disease. Studying HCMV-exposed monocyte-derived dendritic cells by single-cell RNA sequencing, we observe that most cells are entered by the virus, whereas less than 30% of them initiate viral gene expression. Increased viral gene expression is associated with activation of the stimulator of interferon genes (STING) that usually induces anti-viral interferon responses, and with the induction of several pro- (RHOB, HSP1A1, DNAJB1) and anti-viral (RNF213, TNFSF10, IFI16) genes. Upon progression of infection, interferon-beta but not interferon-lambda transcription is inhibited. Similarly, interferon-stimulated gene expression is initially induced and then shut off, thus further promoting productive infection. Monocyte-derived dendritic cells are composed of 3 subsets, with one being especially susceptible to HCMV. In conclusion, HCMV permissiveness of monocyte-derived dendritic cells depends on complex interactions between virus sensing, regulation of the interferon response, and viral gene expression. |
| first_indexed | 2024-03-07T14:51:36Z |
| format | Article |
| id | doaj.art-7e57f2fc99c0427a90c6d097bb173ff7 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-07T14:51:36Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-7e57f2fc99c0427a90c6d097bb173ff72024-03-05T19:40:58ZengNature PortfolioNature Communications2041-17232024-02-0115111610.1038/s41467-024-45614-3Human cytomegalovirus exploits STING signaling and counteracts IFN/ISG induction to facilitate infection of dendritic cellsBibiana Costa0Jennifer Becker1Tobias Krammer2Felix Mulenge3Verónica Durán4Andreas Pavlou5Olivia Luise Gern6Xiaojing Chu7Yang Li8Luka Čičin-Šain9Britta Eiz-Vesper10Martin Messerle11Lars Dölken12Antoine-Emmanuel Saliba13Florian Erhard14Ulrich Kalinke15Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical SchoolInstitute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical SchoolHelmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz-Centre for Infection Research (HZI)Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical SchoolInstitute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical SchoolInstitute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical SchoolInstitute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical SchoolDepartment of Computational Biology for Individualised Medicine, Centre for Individualised Infection Medicine (CiiM) & TWINCORE, a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical SchoolDepartment of Computational Biology for Individualised Medicine, Centre for Individualised Infection Medicine (CiiM) & TWINCORE, a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical SchoolInstitute for Immune Aging and Chronic Infection, Helmholtz Centre for Infection ResearchInstitute for Transfusion Medicine and Transplant Engineering, Hannover Medical SchoolInstitute of Virology, Hannover Medical SchoolInstitute for Virology and Immunobiology, University of WürzburgHelmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz-Centre for Infection Research (HZI)Institute for Virology and Immunobiology, University of WürzburgInstitute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical SchoolAbstract Human cytomegalovirus (HCMV) is a widespread pathogen that in immunocompromised hosts can cause life-threatening disease. Studying HCMV-exposed monocyte-derived dendritic cells by single-cell RNA sequencing, we observe that most cells are entered by the virus, whereas less than 30% of them initiate viral gene expression. Increased viral gene expression is associated with activation of the stimulator of interferon genes (STING) that usually induces anti-viral interferon responses, and with the induction of several pro- (RHOB, HSP1A1, DNAJB1) and anti-viral (RNF213, TNFSF10, IFI16) genes. Upon progression of infection, interferon-beta but not interferon-lambda transcription is inhibited. Similarly, interferon-stimulated gene expression is initially induced and then shut off, thus further promoting productive infection. Monocyte-derived dendritic cells are composed of 3 subsets, with one being especially susceptible to HCMV. In conclusion, HCMV permissiveness of monocyte-derived dendritic cells depends on complex interactions between virus sensing, regulation of the interferon response, and viral gene expression.https://doi.org/10.1038/s41467-024-45614-3 |
| spellingShingle | Bibiana Costa Jennifer Becker Tobias Krammer Felix Mulenge Verónica Durán Andreas Pavlou Olivia Luise Gern Xiaojing Chu Yang Li Luka Čičin-Šain Britta Eiz-Vesper Martin Messerle Lars Dölken Antoine-Emmanuel Saliba Florian Erhard Ulrich Kalinke Human cytomegalovirus exploits STING signaling and counteracts IFN/ISG induction to facilitate infection of dendritic cells Nature Communications |
| title | Human cytomegalovirus exploits STING signaling and counteracts IFN/ISG induction to facilitate infection of dendritic cells |
| title_full | Human cytomegalovirus exploits STING signaling and counteracts IFN/ISG induction to facilitate infection of dendritic cells |
| title_fullStr | Human cytomegalovirus exploits STING signaling and counteracts IFN/ISG induction to facilitate infection of dendritic cells |
| title_full_unstemmed | Human cytomegalovirus exploits STING signaling and counteracts IFN/ISG induction to facilitate infection of dendritic cells |
| title_short | Human cytomegalovirus exploits STING signaling and counteracts IFN/ISG induction to facilitate infection of dendritic cells |
| title_sort | human cytomegalovirus exploits sting signaling and counteracts ifn isg induction to facilitate infection of dendritic cells |
| url | https://doi.org/10.1038/s41467-024-45614-3 |
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