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Fibroblasts are a site of murine cytomegalovirus lytic replication and Stat1-dependent latent persistence in vivo

Author

Listed:
  • Katarzyna M. Sitnik

    (Helmholtz Centre for Infection Research
    University of Veterinary Medicine Vienna)

  • Fran Krstanović

    (University of Rijeka)

  • Natascha Gödecke

    (Helmholtz Centre for Infection Research)

  • Ulfert Rand

    (Helmholtz Centre for Infection Research)

  • Tobias Kubsch

    (Helmholtz Centre for Infection Research)

  • Henrike Maaß

    (Helmholtz Centre for Infection Research)

  • Yeonsu Kim

    (Helmholtz Centre for Infection Research)

  • Ilija Brizić

    (University of Rijeka)

  • Luka Čičin-Šain

    (Helmholtz Centre for Infection Research
    Centre for Individualized Infection Medicine, a joint venture of HZI and MHH
    German Centre for Infection Research (DZIF), Hannover-Braunschweig site)

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.

Suggested Citation

  • Katarzyna M. Sitnik & Fran Krstanović & Natascha Gödecke & Ulfert Rand & Tobias Kubsch & Henrike Maaß & Yeonsu Kim & Ilija Brizić & Luka Čičin-Šain, 2023. "Fibroblasts are a site of murine cytomegalovirus lytic replication and Stat1-dependent latent persistence in vivo," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38449-x
    DOI: 10.1038/s41467-023-38449-x
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    References listed on IDEAS

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    1. Pia-Katharina Tegtmeyer & Julia Spanier & Katharina Borst & Jennifer Becker & André Riedl & Christoph Hirche & Luca Ghita & Jennifer Skerra & Kira Baumann & Stefan Lienenklaus & Marius Doering & Zsolt, 2019. "STING induces early IFN-β in the liver and constrains myeloid cell-mediated dissemination of murine cytomegalovirus," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
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    3. Christian F. Guerrero-Juarez & Priya H. Dedhia & Suoqin Jin & Rolando Ruiz-Vega & Dennis Ma & Yuchen Liu & Kosuke Yamaga & Olga Shestova & Denise L. Gay & Zaixin Yang & Kai Kessenbrock & Qing Nie & Wa, 2019. "Single-cell analysis reveals fibroblast heterogeneity and myeloid-derived adipocyte progenitors in murine skin wounds," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
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