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Human cytomegalovirus exploits STING signaling and counteracts IFN/ISG induction to facilitate infection of dendritic cells

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Listed:
  • Bibiana Costa

    (a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School)

  • Jennifer Becker

    (a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School)

  • Tobias Krammer

    (Helmholtz-Centre for Infection Research (HZI))

  • Felix Mulenge

    (a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School)

  • Verónica Durán

    (a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School)

  • Andreas Pavlou

    (a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School)

  • Olivia Luise Gern

    (a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School)

  • Xiaojing Chu

    (Centre for Individualised Infection Medicine (CiiM) & TWINCORE, a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School)

  • Yang Li

    (Centre for Individualised Infection Medicine (CiiM) & TWINCORE, a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School
    Radboud University Medical Center)

  • Luka Čičin-Šain

    (Helmholtz Centre for Infection Research)

  • Britta Eiz-Vesper

    (Hannover Medical School)

  • Martin Messerle

    (Hannover Medical School)

  • Lars Dölken

    (University of Würzburg)

  • Antoine-Emmanuel Saliba

    (Helmholtz-Centre for Infection Research (HZI)
    Institute of Molecular Infection Biology (IMIB))

  • Florian Erhard

    (University of Würzburg
    University of Regensburg)

  • Ulrich Kalinke

    (a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School
    Hannover Medical School)

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.

Suggested Citation

  • 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 , 2024. "Human cytomegalovirus exploits STING signaling and counteracts IFN/ISG induction to facilitate infection of dendritic cells," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45614-3
    DOI: 10.1038/s41467-024-45614-3
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    References listed on IDEAS

    as
    1. Florian Erhard & Marisa A. P. Baptista & Tobias Krammer & Thomas Hennig & Marius Lange & Panagiota Arampatzi & Christopher S. Jürges & Fabian J. Theis & Antoine-Emmanuel Saliba & Lars Dölken, 2019. "scSLAM-seq reveals core features of transcription dynamics in single cells," Nature, Nature, vol. 571(7765), pages 419-423, July.
    2. Gioele La Manno & Ruslan Soldatov & Amit Zeisel & Emelie Braun & Hannah Hochgerner & Viktor Petukhov & Katja Lidschreiber & Maria E. Kastriti & Peter Lönnerberg & Alessandro Furlan & Jean Fan & Lars E, 2018. "RNA velocity of single cells," Nature, Nature, vol. 560(7719), pages 494-498, August.
    3. Fabien Thery & Lia Martina & Caroline Asselman & Yifeng Zhang & Madeleine Vessely & Heidi Repo & Koen Sedeyn & George D. Moschonas & Clara Bredow & Qi Wen Teo & Jingshu Zhang & Kevin Leandro & Denzel , 2021. "Ring finger protein 213 assembles into a sensor for ISGylated proteins with antimicrobial activity," Nature Communications, Nature, vol. 12(1), pages 1-21, December.
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