Reversible silencing of cytomegalovirus genomes by type I interferon governs virus latency.
Average rating
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Star rating
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Authors
Dağ, FranziskaDölken, Lars
Holzki, Julia
Drabig, Anja
Weingärtner, Adrien
Schwerk, Johannes
Lienenklaus, Stefan
Conte, Ianina
Geffers, Robert

Davenport, Colin
Rand, Ulfert
Köster, Mario
Weiß, Siegfried
Adler, Barbara
Wirth, Dagmar
Messerle, Martin
Hauser, Hansjörg
Cičin-Šain, Luka
Issue Date
2014-02
Metadata
Show full item recordAbstract
Herpesviruses establish a lifelong latent infection posing the risk for virus reactivation and disease. In cytomegalovirus infection, expression of the major immediate early (IE) genes is a critical checkpoint, driving the lytic replication cycle upon primary infection or reactivation from latency. While it is known that type I interferon (IFN) limits lytic CMV replication, its role in latency and reactivation has not been explored. In the model of mouse CMV infection, we show here that IFNβ blocks mouse CMV replication at the level of IE transcription in IFN-responding endothelial cells and fibroblasts. The IFN-mediated inhibition of IE genes was entirely reversible, arguing that the IFN-effect may be consistent with viral latency. Importantly, the response to IFNβ is stochastic, and MCMV IE transcription and replication were repressed only in IFN-responsive cells, while the IFN-unresponsive cells remained permissive for lytic MCMV infection. IFN blocked the viral lytic replication cycle by upregulating the nuclear domain 10 (ND10) components, PML, Sp100 and Daxx, and their knockdown by shRNA rescued viral replication in the presence of IFNβ. Finally, IFNβ prevented MCMV reactivation from endothelial cells derived from latently infected mice, validating our results in a biologically relevant setting. Therefore, our data do not only define for the first time the molecular mechanism of IFN-mediated control of CMV infection, but also indicate that the reversible inhibition of the virus lytic cycle by IFNβ is consistent with the establishment of CMV latency.Citation
Reversible silencing of cytomegalovirus genomes by type I interferon governs virus latency. 2014, 10 (2):e1003962 PLoS Pathog.Affiliation
Helmholtz Centre for infection research, Inhoffenstr. 7, D-38124 Braunschweig, Germany.Journal
PLoS pathogensPubMed ID
24586165Type
ArticleLanguage
enISSN
1553-7374ae974a485f413a2113503eed53cd6c53
10.1371/journal.ppat.1003962
Scopus Count
Collections
The following license files are associated with this item:
Related articles
- Type I Interferon Released by Myeloid Dendritic Cells Reversibly Impairs Cytomegalovirus Replication by Inhibiting Immediate Early Gene Expression.
- Authors: Holzki JK, Dağ F, Dekhtiarenko I, Rand U, Casalegno-Garduño R, Trittel S, May T, Riese P, Čičin-Šain L
- Issue date: 2015 Oct
- Human cytomegalovirus gene expression is silenced by Daxx-mediated intrinsic immune defense in model latent infections established in vitro.
- Authors: Saffert RT, Kalejta RF
- Issue date: 2007 Sep
- Inhibition of the Super Elongation Complex Suppresses Herpes Simplex Virus Immediate Early Gene Expression, Lytic Infection, and Reactivation from Latency.
- Authors: Alfonso-Dunn R, Arbuckle JH, Vogel JL, Kristie TM
- Issue date: 2020 Jun 9
- Human cytomegalovirus major immediate early transcripts arise predominantly from the canonical major immediate early promoter in reactivating progenitor-derived dendritic cells.
- Authors: Mason R, Groves IJ, Wills MR, Sinclair JH, Reeves MB
- Issue date: 2020 Jun
- An epistatic relationship between the viral protein kinase UL97 and the UL133-UL138 latency locus during the human cytomegalovirus lytic cycle.
- Authors: Li G, Rak M, Nguyen CC, Umashankar M, Goodrum FD, Kamil JP
- Issue date: 2014 Jun