Journal Article

DZNE-2026-01006

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png IFI16 restricts SARS-CoV-2 replication by disrupting nucleocapsid-driven phase separation.

Cislaghi, I. ; Turati, S. ; Vicario, D. ; Griffante, G. ; Chandel, S. ; Lo Cigno, I. ; Bizzarri, R. ; Storti, B. ; Ukmar Godec, T.DZNE* ; Zachrdla, M.DZNE* ; Zweckstetter, M.DZNE* ; Signorini, L. ; Maina, K. K. ; Delbue, S. ; Borgogna, C. ; Gariglio, M.

2026
Springer Nature London

This record in other databases:    

Please use a persistent id in citations: 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.

Keyword(s): Humans (MeSH) ; Phosphoproteins: metabolism (MeSH) ; Phosphoproteins: genetics (MeSH) ; Virus Replication (MeSH) ; SARS-CoV-2: physiology (MeSH) ; SARS-CoV-2: genetics (MeSH) ; Nuclear Proteins: metabolism (MeSH) ; Nuclear Proteins: genetics (MeSH) ; Phase Separation (MeSH) ; Nucleocapsid: metabolism (MeSH) ; RNA, Viral: metabolism (MeSH) ; Animals (MeSH) ; Coronavirus Nucleocapsid Proteins: metabolism (MeSH) ; COVID-19: virology (MeSH) ; COVID-19: metabolism (MeSH) ; Phosphoproteins ; IFI16 protein, human ; Nuclear Proteins ; RNA, Viral ; Coronavirus Nucleocapsid Proteins

---

Contributing Institute(s):

1. Translational Structural Biology (AG Zweckstetter)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2026

---

Database coverage:
; ; ; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

---