Reversible silencing of cytomegalovirus genomes by type I interferon governs virus latency.
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AbstractHerpesviruses 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.
CitationReversible silencing of cytomegalovirus genomes by type I interferon governs virus latency. 2014, 10 (2):e1003962 PLoS Pathog.
AffiliationHelmholtz Centre for infection research, Inhoffenstr. 7, D-38124 Braunschweig, Germany.
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- Type I Interferon Released by Myeloid Dendritic Cells Reversibly Impairs Cytomegalovirus Replication by Inhibiting Immediate Early Gene Expression.
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- 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
- An epistatic relationship between the viral protein kinase UL97 and the UL133-UL138 latency locus during the human cytomegalovirus lytic cycle.
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- A myeloid progenitor cell line capable of supporting human cytomegalovirus latency and reactivation, resulting in infectious progeny.
- Authors: O'Connor CM, Murphy EA
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- Human cytomegalovirus modulates monocyte-mediated innate immune responses during short-term experimental latency in vitro.
- Authors: Noriega VM, Haye KK, Kraus TA, Kowalsky SR, Ge Y, Moran TM, Tortorella D
- Issue date: 2014 Aug