Journal Article

DKFZ-2025-00144

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Herpesviruses mimic zygotic genome activation to promote viral replication.

Neugebauer, E. ; Walter, S. ; Tan, J. ; Drayman, N. ; Franke, V. ; van Gent, M. ; Pennisi, S. ; Veratti, P. ; Stein, K. S. ; Welker, I. ; Tay, S. ; Verjans, G. M. G. M. ; Timmers, H. T. M.DKFZ* ; Akalin, A. ; Landthaler, M. ; Ensser, A. ; Wyler, E. ; Full, F.

2025
Springer Nature [London]

This record in other databases:  

Please use a persistent id in citations: doi:10.1038/s41467-025-55928-5

Abstract: Zygotic genome activation (ZGA) is crucial for maternal to zygotic transition at the 2-8-cell stage in order to overcome silencing of genes and enable transcription from the zygotic genome. In humans, ZGA is induced by DUX4, a pioneer factor that drives expression of downstream germline-specific genes and retroelements. Here we show that herpesviruses from all subfamilies, papillomaviruses and Merkel cell polyomavirus actively induce DUX4 expression to promote viral transcription and replication. Analysis of single-cell sequencing data sets from patients shows that viral DUX4 activation is of relevance in vivo. Herpes-simplex virus 1 (HSV-1) immediate early proteins directly induce expression of DUX4 and its target genes, which mimics zygotic genome activation. Upon HSV-1 infection, DUX4 directly binds to the viral genome and promotes viral transcription. DUX4 is functionally required for infection, since genetic depletion by CRISPR/Cas9 as well as degradation of DUX4 by nanobody constructs abrogates HSV-1 replication. Our results show that DNA viruses including herpesviruses mimic an embryonic-like transcriptional program that prevents epigenetic silencing of the viral genome and facilitates herpesviral gene expression.

Keyword(s): Virus Replication: genetics (MeSH) ; Humans (MeSH) ; Zygote: metabolism (MeSH) ; Zygote: virology (MeSH) ; Herpesvirus 1, Human: genetics (MeSH) ; Herpesvirus 1, Human: physiology (MeSH) ; Genome, Viral (MeSH) ; Homeodomain Proteins: metabolism (MeSH) ; Homeodomain Proteins: genetics (MeSH) ; Herpesviridae: genetics (MeSH) ; Herpesviridae: physiology (MeSH) ; Gene Expression Regulation, Viral (MeSH) ; Animals (MeSH) ; HEK293 Cells (MeSH) ; Merkel cell polyomavirus: genetics (MeSH) ; Homeodomain Proteins

---

Contributing Institute(s):

1. DKTK Koordinierungsstelle Freiburg (FR01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2025

---

Database coverage:
; ; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 15 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

---