2. Academic Validation
  3. IFI16 restricts SARS-CoV-2 replication by disrupting nucleocapsid-driven phase separation

IFI16 restricts SARS-CoV-2 replication by disrupting nucleocapsid-driven phase separation

  • Commun Biol. 2026 Jun 1. doi: 10.1038/s42003-026-10363-0.
Ilaria Cislaghi 1,  Sarah Turati 1,  Dalila Vicario 1,  Gloria Griffante 1 2,  Shikha Chandel 1,  Irene Lo Cigno 1,  Ranieri Bizzarri 3 4 5,  Barbara Storti 5,  Tina Ukmar Godec 6,  Milan Zachrdla 6,  Markus Zweckstetter 6 7,  Lucia Signorini 8,  Kevin Kamau Maina 8,  Serena Delbue 8,  Cinzia Borgogna 9,  Marisa Gariglio 10
Affiliations

Affiliations

  • 1 Virology Unit, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy.
  • 2 Department of Public Health and Pediatric Sciences, University of Turin, Turin, Italy.
  • 3 Department of Surgical, Medical, Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy.
  • 4 Center for Instrument Sharing of the University of Pisa (CISUP), University of Pisa, Pisa, Italy.
  • 5 Istituto Nanoscienze, CNR, NEST-SNS, Pisa, Italy.
  • 6 German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
  • 7 Department for NMR-based Structural Biology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
  • 8 Laboratory of Molecular Virology, Department of Biomedical, Surgical and Dental Sciences, University of Milano, Milano, Italy.
  • 9 Virology Unit, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy. [email protected].
  • 10 Virology Unit, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy. [email protected].
PMID: 42225939 DOI: 10.1038/s42003-026-10363-0
Abstract

IFI16 is an interferon-inducible protein that senses viral DNA and can also restrict RNA virus replication. Here, using IFI16 knockout cellular models, we identify IFI16 as a host restriction factor that limits SARS-CoV-2 replication. Upon SARS-CoV-2 Infection, IFI16 relocalizes from the nucleus to the cytoplasm, where it binds both the nucleocapsid protein and the viral genome. This impairs SARS-CoV-2 replication by inhibiting viral RNA-induced condensate formation of the nucleocapsid protein. Finally, we extend our analysis to Other human coronaviruses and observe that IFI16 depletion also enhances OC43 replication, whereas it is associated with reduced NL63 replication, highlighting a differential, virus-specific effect of IFI16 on coronavirus infections. Overall, these findings provide mechanistic insights into how the absence of IFI16 creates a cellular environment that supports SARS-CoV-2 replication.

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