Fibroblasts are a site of murine cytomegalovirus lytic replication and Stat1-dependent latent persistence in vivo
Abstract To date, no herpesvirus has been shown to latently persist in fibroblastic cells. Here, we show that murine cytomegalovirus, a β-herpesvirus, persists for the long term and across organs in PDGFRα-positive fibroblastic cells, with similar or higher genome loads than in the previously known...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-38449-x |
| _version_ | 1797811397899321344 |
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| author | Katarzyna M. Sitnik Fran Krstanović Natascha Gödecke Ulfert Rand Tobias Kubsch Henrike Maaß Yeonsu Kim Ilija Brizić Luka Čičin-Šain |
| author_facet | Katarzyna M. Sitnik Fran Krstanović Natascha Gödecke Ulfert Rand Tobias Kubsch Henrike Maaß Yeonsu Kim Ilija Brizić Luka Čičin-Šain |
| author_sort | Katarzyna M. Sitnik |
| collection | DOAJ |
| description | Abstract To date, no herpesvirus has been shown to latently persist in fibroblastic cells. Here, we show that murine cytomegalovirus, a β-herpesvirus, persists for the long term and across organs in PDGFRα-positive fibroblastic cells, with similar or higher genome loads than in the previously known sites of murine cytomegalovirus latency. Whereas murine cytomegalovirus gene transcription in PDGFRα-positive fibroblastic cells is almost completely silenced at 5 months post-infection, these cells give rise to reactivated virus ex vivo, arguing that they support latent murine cytomegalovirus infection. Notably, PDGFRα-positive fibroblastic cells also support productive virus replication during primary murine cytomegalovirus infection. Mechanistically, Stat1-deficiency promotes lytic infection but abolishes latent persistence of murine cytomegalovirus in PDGFRα-positive fibroblastic cells in vivo. In sum, fibroblastic cells have a dual role as a site of lytic murine cytomegalovirus replication and a reservoir of latent murine cytomegalovirus in vivo and STAT1 is required for murine cytomegalovirus latent persistence in vivo. |
| first_indexed | 2024-03-13T07:22:03Z |
| format | Article |
| id | doaj.art-420af61a8cd44f1fa7f5b9f132fd1f4a |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-13T07:22:03Z |
| publishDate | 2023-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-420af61a8cd44f1fa7f5b9f132fd1f4a2023-06-04T11:33:38ZengNature PortfolioNature Communications2041-17232023-05-0114111310.1038/s41467-023-38449-xFibroblasts are a site of murine cytomegalovirus lytic replication and Stat1-dependent latent persistence in vivoKatarzyna M. Sitnik0Fran Krstanović1Natascha Gödecke2Ulfert Rand3Tobias Kubsch4Henrike Maaß5Yeonsu Kim6Ilija Brizić7Luka Čičin-Šain8Department of Viral Immunology, Helmholtz Centre for Infection ResearchCenter for Proteomics, Faculty of Medicine, University of RijekaDepartment of Viral Immunology, Helmholtz Centre for Infection ResearchDepartment of Viral Immunology, Helmholtz Centre for Infection ResearchDepartment of Viral Immunology, Helmholtz Centre for Infection ResearchDepartment of Viral Immunology, Helmholtz Centre for Infection ResearchDepartment of Viral Immunology, Helmholtz Centre for Infection ResearchCenter for Proteomics, Faculty of Medicine, University of RijekaDepartment of Viral Immunology, Helmholtz Centre for Infection ResearchAbstract To date, no herpesvirus has been shown to latently persist in fibroblastic cells. Here, we show that murine cytomegalovirus, a β-herpesvirus, persists for the long term and across organs in PDGFRα-positive fibroblastic cells, with similar or higher genome loads than in the previously known sites of murine cytomegalovirus latency. Whereas murine cytomegalovirus gene transcription in PDGFRα-positive fibroblastic cells is almost completely silenced at 5 months post-infection, these cells give rise to reactivated virus ex vivo, arguing that they support latent murine cytomegalovirus infection. Notably, PDGFRα-positive fibroblastic cells also support productive virus replication during primary murine cytomegalovirus infection. Mechanistically, Stat1-deficiency promotes lytic infection but abolishes latent persistence of murine cytomegalovirus in PDGFRα-positive fibroblastic cells in vivo. In sum, fibroblastic cells have a dual role as a site of lytic murine cytomegalovirus replication and a reservoir of latent murine cytomegalovirus in vivo and STAT1 is required for murine cytomegalovirus latent persistence in vivo.https://doi.org/10.1038/s41467-023-38449-x |
| spellingShingle | Katarzyna M. Sitnik Fran Krstanović Natascha Gödecke Ulfert Rand Tobias Kubsch Henrike Maaß Yeonsu Kim Ilija Brizić Luka Čičin-Šain Fibroblasts are a site of murine cytomegalovirus lytic replication and Stat1-dependent latent persistence in vivo Nature Communications |
| title | Fibroblasts are a site of murine cytomegalovirus lytic replication and Stat1-dependent latent persistence in vivo |
| title_full | Fibroblasts are a site of murine cytomegalovirus lytic replication and Stat1-dependent latent persistence in vivo |
| title_fullStr | Fibroblasts are a site of murine cytomegalovirus lytic replication and Stat1-dependent latent persistence in vivo |
| title_full_unstemmed | Fibroblasts are a site of murine cytomegalovirus lytic replication and Stat1-dependent latent persistence in vivo |
| title_short | Fibroblasts are a site of murine cytomegalovirus lytic replication and Stat1-dependent latent persistence in vivo |
| title_sort | fibroblasts are a site of murine cytomegalovirus lytic replication and stat1 dependent latent persistence in vivo |
| url | https://doi.org/10.1038/s41467-023-38449-x |
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