Myeloid dendritic cells repress human cytomegalovirus gene expression and spread by releasing interferon-unrelated soluble antiviral factors.
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.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Vondran, Florian W R
MetadataShow full item record
AbstractCytomegalovirus (CMV) is a beta-herpesvirus that latently infects most adult humans worldwide and is a major cause of morbidity and mortality in immunocompromised hosts. Latent human CMV (HCMV) is believed to reside in precursors of myeloid-lineage, leukocytes and monocytes, which give raise to macrophages and dendritic cells. We report here that human monocyte derived DCs (mo-DC) suppress HCMV infection in coculture with infected fibroblasts target cells in an effector-to-target-ratio dependent manner. Intriguingly, optimal activation of mo-DC was achieved in coculture conditions, not by their direct infection with HCMV, implying that mo-DC may recognize unique molecular patterns on, or within, infected fibroblasts. We show that HCMV is controlled by secreted factors that act by priming defenses in target cells rather than by direct viral neutralization, but we excluded a role for IFNs in this control. The expression of lytic viral genes in infected cells and the progression of infection were significantly slowed down, but this effect was reversible, indicating that the control of infection depended on the transient induction of antiviral effector molecules in target cells. Using immediate-early or late-phase reporter HCMVs, we show that soluble factors secreted in the cocultures suppress HCMV replication at both stages of the infection and that their antiviral effect is robust and comparable in numerous batches of mo-DCs as well as in primary fibroblasts and stromal cells.Importance Human cytomegalovirus is a widespread opportunistic pathogen that can cause severe disease and complications in vulnerable individuals. This includes newborn children, HIV AIDS patients or transplant recipients. Although the majority of healthy humans carry this virus throughout their lives without symptoms, it is not exactly clear which tissues in the body are the main reservoirs of latent virus infection, or how the delicate balance between the virus and the immune system is maintained over the individual's lifetime. Here for the first time, we provide evidence for a novel mechanism of direct virus control by a subset of human innate immune cells called Dendritic Cells, which are regarded as a major site of virus latency and reactivation. Our findings may have important implications in HCMV disease prevention as well as development of novel therapeutic approaches.
CitationMyeloid dendritic cells repress human cytomegalovirus gene expression and spread by releasing interferon-unrelated soluble antiviral factors. 2017 J. Virol.
AffiliationHelmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.
JournalJournal of virology
The following license files are associated with this item:
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-sa/4.0/
- 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 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
- Latency-Associated Expression of Human Cytomegalovirus US28 Attenuates Cell Signaling Pathways To Maintain Latent Infection.
- Authors: Krishna BA, Poole EL, Jackson SE, Smit MJ, Wills MR, Sinclair JH
- Issue date: 2017 Dec 5
- Human cytomegalovirus: Latency and reactivation in the myeloid lineage.
- Authors: Sinclair J
- Issue date: 2008 Mar
- Circulating dendritic cells isolated from healthy seropositive donors are sites of human cytomegalovirus reactivation in vivo.
- Authors: Reeves MB, Sinclair JH
- Issue date: 2013 Oct