The targeted cytosolic degradation of class I histone deacetylases is essential for efficient alphaherpesvirus replication.

Authors

Shengli-Li Ming, Meng-Hua Du, Jia-Ming Yang, Ya-Di Guo, Jia-Jia Pan, Wei-Fei Lu, Jiang Wang, Lei Zeng, Bei-Bei Chu

Published in

eLife. Volume 15. Jul 09, 2026. Epub Jul 09, 2026.

Abstract

Viral infection triggers a robust DNA damage response (DDR), reshaping the host chromatin landscape to facilitate viral replication. Here, we uncover a novel mechanism by which alphaherpesviruses exploit the DDR pathway. We demonstrated that herpes simplex virus 1 (HSV-1) and pseudorabies virus (PRV) induced selective degradation of class I histone deacetylases (HDAC1/2), leading to histone hyperacetylation and subsequent DDR activation. Strikingly, viral infection promoted nuclear export of HDAC1/2, followed by MDM2-mediated K63-linked polyubiquitination and proteasomal degradation in the cytoplasm. Pharmacological inhibition of either DDR signaling or HDAC1/2 nuclear export significantly affected viral replication in vitro and in vivo. Our findings reveal a unique viral strategy to hijack host epigenetic regulation for efficient replication, and identify potential therapeutic targets for alphaherpesvirus infections.

PMID:
42423462
Bibliographic data and abstract were imported from PubMed on 09 Jul 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.