Prefoldin complex promotes interferon-stimulated gene expression and is inhibited by rotavirus VP3

Yinxing Zhu, Yanhua Song, Dilip Kumar, Peter K. Jackson, B. V. Venkataram Prasad and Siyuan Ding ()
Additional contact information
Yinxing Zhu: Washington University School of Medicine
Yanhua Song: Stanford School of Medicine
Dilip Kumar: Baylor College of Medicine
Peter K. Jackson: Stanford School of Medicine
B. V. Venkataram Prasad: Baylor College of Medicine
Siyuan Ding: Washington University School of Medicine

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: Abstract Timely induction of interferons and interferon-stimulated genes (ISGs) is critical for successful host defense against viral infections. VP3 encoded by rotavirus is implicated in interferon antagonism. However, the precise mechanisms remain incompletely understood. By conducting tandem-affinity purification coupled with high-resolution mass spectrometry, we identify the prefoldin complex as the top cellular binding partner of VP3. Rotavirus infection is significantly enhanced in prefoldin subunit knockout cells. Using proteome-wide label-free quantification, we find that prefoldin assists in folding ubiquitin-like-modifier-activating-enzyme-3 (UBA3), both of which positively regulate ISG expression. Through direct and competitive binding, VP3 interferes with the chaperone activity of prefoldin, leading to unstable UBA3, reduces IRF9, and suppresses ISG transcription. Our findings report a novel function of a prefoldin-UBA3-IRF9-ISG axis in antiviral immunity and uncover new aspects of virus-host interactions that could be exploited for broad-spectrum antiviral therapeutic development.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-63393-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63393-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-63393-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().