title: The small noncoding RNAs (sncRNAs) of murine gammaherpesvirus 68 (MHV-68) are involved in regulating the latent-to-lytic switch in vivo.
abstract: The human gammaherpesviruses Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), which are associated with a variety of diseases including tumors, produce various small noncoding RNAs (sncRNAs) such as microRNAs (miRNAs). Like all herpesviruses, they show two stages in their life cycle: lytic replication and latency. During latency, hardly any viral proteins are expressed to avoid recognition by the immune system. Thus, sncRNAs might be exploited since they are less likely to be recognized. Specifically, it has been proposed that sncRNAs might contribute to the maintenance of latency. This has already been shown in vitro, but the respective evidence in vivo is very limited. A natural model system to explore this question in vivo is infection of mice with murine gammaherpesvirus 68 (MHV-68). We used this model to analyze a MHV-68 mutant lacking the expression of all miRNAs. In the absence of the miRNAs, we observed a higher viral genomic load during late latency in the spleens of mice. We propose that this is due to a disturbed regulation of the latent-to-lytic switch, altering the balance between latent and lytic infection. Hence, we provide for the first time evidence that gammaherpesvirus sncRNAs contribute to the maintenance of latency in vivo.
authors: Comprehensive Pneumology Center, Research Unit Lung Repair and Regeneration, Helmholtz Zentrum München - German Research Center for Environmental Health (GmbH), Member of the German Center of Lung Research (DZL), Marchioninistrasse 25, D-81377 Munich, Germany.
authors: Beatrix
authors: B
authors: Steer
authors: Comprehensive Pneumology Center, Research Unit Lung Repair and Regeneration, Helmholtz Zentrum München - German Research Center for Environmental Health (GmbH), Member of the German Center of Lung Research (DZL), Marchioninistrasse 25, D-81377 Munich, Germany.
authors: Martin
authors: M
authors: Strehle
authors: Comprehensive Pneumology Center, Research Unit Lung Repair and Regeneration, Helmholtz Zentrum München - German Research Center for Environmental Health (GmbH), Member of the German Center of Lung Research (DZL), Marchioninistrasse 25, D-81377 Munich, Germany.|Institute of Lung Biology and Disease, Comprehensive Pneumology Center, Helmholtz Zentrum München - German Research Center for Environmental Health (GmbH), Member of the German Center of Lung Research (DZL), Ingolstädter Landstrasse 1, D-85764 Neuherberg, Germany.
authors: Christine
authors: C
authors: Sattler
authors: Comprehensive Pneumology Center, Research Unit Lung Repair and Regeneration, Helmholtz Zentrum München - German Research Center for Environmental Health (GmbH), Member of the German Center of Lung Research (DZL), Marchioninistrasse 25, D-81377 Munich, Germany.
authors: Dagmar
authors: D
authors: Bund
authors: Comprehensive Pneumology Center, Research Unit Lung Repair and Regeneration, Helmholtz Zentrum München - German Research Center for Environmental Health (GmbH), Member of the German Center of Lung Research (DZL), Marchioninistrasse 25, D-81377 Munich, Germany.
authors: Britta
authors: B
authors: Flach
authors: Institute of Lung Biology and Disease, Comprehensive Pneumology Center, Helmholtz Zentrum München - German Research Center for Environmental Health (GmbH), Member of the German Center of Lung Research (DZL), Ingolstädter Landstrasse 1, D-85764 Neuherberg, Germany.
authors: Tobias
authors: T
authors: Stoeger
authors: Division of Infection and Pathway Medicine, University of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, UK.
authors: Jürgen G
authors: JG
authors: Haas
authors: Comprehensive Pneumology Center, Research Unit Lung Repair and Regeneration, Helmholtz Zentrum München - German Research Center for Environmental Health (GmbH), Member of the German Center of Lung Research (DZL), Marchioninistrasse 25, D-81377 Munich, Germany.
authors: Heiko
authors: H
authors: Adler
mesh_terms: D000818:Animals; D006224:Cricetinae; D006566:Herpesviridae Infections / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D041681:NIH 3T3 Cells; D058727:RNA, Small Untranslated / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D018144:Rhadinovirus / Q000502:physiology*; D017735:Virus Latency / Q000502:physiology*
chemical_list: D058727:RNA, Small Untranslated; D012367:RNA, Viral