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000297967 1001_ $$00009-0009-6298-5267$$aNeugebauer, Eva$$b0
000297967 245__ $$aHerpesviruses mimic zygotic genome activation to promote viral replication.
000297967 260__ $$a[London]$$bSpringer Nature$$c2025
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000297967 520__ $$aZygotic 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.
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000297967 650_7 $$2NLM Chemicals$$aHomeodomain Proteins
000297967 650_2 $$2MeSH$$aVirus Replication: genetics
000297967 650_2 $$2MeSH$$aHumans
000297967 650_2 $$2MeSH$$aZygote: metabolism
000297967 650_2 $$2MeSH$$aZygote: virology
000297967 650_2 $$2MeSH$$aHerpesvirus 1, Human: genetics
000297967 650_2 $$2MeSH$$aHerpesvirus 1, Human: physiology
000297967 650_2 $$2MeSH$$aGenome, Viral
000297967 650_2 $$2MeSH$$aHomeodomain Proteins: metabolism
000297967 650_2 $$2MeSH$$aHomeodomain Proteins: genetics
000297967 650_2 $$2MeSH$$aHerpesviridae: genetics
000297967 650_2 $$2MeSH$$aHerpesviridae: physiology
000297967 650_2 $$2MeSH$$aGene Expression Regulation, Viral
000297967 650_2 $$2MeSH$$aAnimals
000297967 650_2 $$2MeSH$$aHEK293 Cells
000297967 650_2 $$2MeSH$$aMerkel cell polyomavirus: genetics
000297967 7001_ $$aWalter, Stephanie$$b1
000297967 7001_ $$00009-0005-8827-3533$$aTan, Jiang$$b2
000297967 7001_ $$aDrayman, Nir$$b3
000297967 7001_ $$00000-0003-3606-6792$$aFranke, Vedran$$b4
000297967 7001_ $$00000-0003-3798-5360$$avan Gent, Michiel$$b5
000297967 7001_ $$aPennisi, Sandra$$b6
000297967 7001_ $$aVeratti, Pia$$b7
000297967 7001_ $$aStein, Karla S$$b8
000297967 7001_ $$00009-0007-9507-3622$$aWelker, Isabelle$$b9
000297967 7001_ $$00000-0002-1912-6020$$aTay, Savaş$$b10
000297967 7001_ $$00000-0002-2465-2674$$aVerjans, Georges M G M$$b11
000297967 7001_ $$0P:(DE-He78)a77f61c7d4ca6aa1f9adc620eed66f3d$$aTimmers, Hermanus Theodorus Marcus$$b12$$udkfz
000297967 7001_ $$00000-0002-0468-0117$$aAkalin, Altuna$$b13
000297967 7001_ $$00000-0002-1075-8734$$aLandthaler, Markus$$b14
000297967 7001_ $$00000-0001-8873-3863$$aEnsser, Armin$$b15
000297967 7001_ $$00000-0002-9884-1806$$aWyler, Emanuel$$b16
000297967 7001_ $$00000-0003-1900-5891$$aFull, Florian$$b17
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