Herpesviruses mimic zygotic genome activation to promote viral replication

• DOI: 10.1038/s41467-025-55928-5
• Publication Date: 2025-01-15T23:27:16Z
• Authors: Eva Neugebauer; Stephanie Walter; Jiang Tan; Nir Drayman; Vedran Franke; Michiel van Gent; Sandra Pennisi; Pia Veratti; Karla S. Stein; Isabelle Welker; Savaş Tay; Georges M. G. M. ...; H. T. Marc Timmers; Altuna Akalin; Markus Landthaler; Armin Ensser; Emanuel Wyler; Florian Full
• Keywords: Replication

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