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| Item Type: | Article |
|---|---|
| Title: | Herpesviruses mimic zygotic genome activation to promote viral replication |
| Creators Name: | 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., Akalin, A., Landthaler, M., Ensser, A., Wyler, E. and Full, F. |
| 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. |
| Keywords: | HEK293 Cells, Herpesviridae, Homeodomain Proteins, Human Herpesvirus 1, Merkel Cell Polyomavirus, Viral Gene Expression Regulation, Viral Genome, Virus Replication, Zygote, Animals |
| Source: | Nature Communications |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Volume: | 16 |
| Number: | 1 |
| Page Range: | 710 |
| Date: | 16 January 2025 |
| Official Publication: | https://doi.org/10.1038/s41467-025-55928-5 |
| PubMed: | View item in PubMed |
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