Human cytomegalovirus exploits STING signaling and counteracts IFN/ISG induction to facilitate infection of dendritic cells
© 2024. The Author(s)..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Nature communications - 15(2024), 1 vom: 26. Feb., Seite 1745 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Costa, Bibiana [VerfasserIn] |
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| Links: |
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| Themen: |
9008-11-1 |
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| Anmerkungen: |
Date Completed 28.02.2024 Date Revised 29.02.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41467-024-45614-3 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM368991008 |
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| 520 | |a © 2024. The Author(s). | ||
| 520 | |a 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 | ||
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| 700 | 1 | |a Becker, Jennifer |e verfasserin |4 aut | |
| 700 | 1 | |a Krammer, Tobias |e verfasserin |4 aut | |
| 700 | 1 | |a Mulenge, Felix |e verfasserin |4 aut | |
| 700 | 1 | |a Durán, Verónica |e verfasserin |4 aut | |
| 700 | 1 | |a Pavlou, Andreas |e verfasserin |4 aut | |
| 700 | 1 | |a Gern, Olivia Luise |e verfasserin |4 aut | |
| 700 | 1 | |a Chu, Xiaojing |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Čičin-Šain, Luka |e verfasserin |4 aut | |
| 700 | 1 | |a Eiz-Vesper, Britta |e verfasserin |4 aut | |
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| 700 | 1 | |a Erhard, Florian |e verfasserin |4 aut | |
| 700 | 1 | |a Kalinke, Ulrich |e verfasserin |4 aut | |
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