{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Schwerk J"],"funding":["Deutsche Forschungsgemeinschaft","German Ministry of Education and Research","Niedersächsisches Ministerium für Wissenschaft und Kultur"],"pagination":["1554"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9787724"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["11(12)"],"pubmed_abstract":["Gammaherpesviruses, such as Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus, are important human pathogens involved in lymphoproliferative disorders and tumorigenesis. Herpesvirus infections are characterized by a biphasic cycle comprised of an acute phase with lytic replication and a latent state. Murine gammaherpesvirus 68 (MHV-68) is a well-established model for the study of lytic and latent life cycles in the mouse. We investigated the interplay between the type I interferon (IFN)-mediated innate immune response and MHV-68 latency using sensitive bioluminescent reporter mice. Adoptive transfer of latently infected splenocytes into type I IFN receptor-deficient mice led to a loss of latency control. This was revealed by robust viral propagation and dissemination of MHV-68, which coincided with type I IFN reporter induction. Despite MHV-68 latency control by IFN, the continuous low-level cell-to-cell transmission of MHV-68 was detected in the presence of IFN signaling, indicating that IFN cannot fully prevent viral dissemination during latency. Moreover, impaired type I IFN signaling in latently infected splenocytes increased the risk of virus reactivation, demonstrating that IFN directly controls MHV-68 latency in infected cells. Overall, our data show that locally constrained type I IFN responses control the cellular reservoir of latency, as well as the distribution of latent infection to potential new target cells."],"journal":["Pathogens (Basel, Switzerland)"],"pubmed_title":["Type I Interferon Signaling Controls Gammaherpesvirus Latency In Vivo."],"pmcid":["PMC9787724"],"funding_grant_id":["Cluster of Excellence REBIRTH; research grant Ho 2236/8-1; SPP1656; Collaborative Research Center SFB900","80029155","01KI1003D"],"pubmed_authors":["Brinkmann MM","Lienenklaus S","Cicin-Sain L","Koster M","Kalinke U","Schwerk J","Kroger A","Hauser H","Kemper L","Bussey KA","Messerle M","Weiss S","Collins CM","Speck SH","Wirth D"],"additional_accession":[]},"is_claimable":false,"name":"Type I Interferon Signaling Controls Gammaherpesvirus Latency In Vivo.","description":"Gammaherpesviruses, such as Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus, are important human pathogens involved in lymphoproliferative disorders and tumorigenesis. Herpesvirus infections are characterized by a biphasic cycle comprised of an acute phase with lytic replication and a latent state. Murine gammaherpesvirus 68 (MHV-68) is a well-established model for the study of lytic and latent life cycles in the mouse. We investigated the interplay between the type I interferon (IFN)-mediated innate immune response and MHV-68 latency using sensitive bioluminescent reporter mice. Adoptive transfer of latently infected splenocytes into type I IFN receptor-deficient mice led to a loss of latency control. This was revealed by robust viral propagation and dissemination of MHV-68, which coincided with type I IFN reporter induction. Despite MHV-68 latency control by IFN, the continuous low-level cell-to-cell transmission of MHV-68 was detected in the presence of IFN signaling, indicating that IFN cannot fully prevent viral dissemination during latency. Moreover, impaired type I IFN signaling in latently infected splenocytes increased the risk of virus reactivation, demonstrating that IFN directly controls MHV-68 latency in infected cells. Overall, our data show that locally constrained type I IFN responses control the cellular reservoir of latency, as well as the distribution of latent infection to potential new target cells.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Dec","modification":"2025-04-22T04:50:51.243Z","creation":"2025-04-05T21:04:02.168Z"},"accession":"S-EPMC9787724","cross_references":{"pubmed":["36558888"],"doi":["10.3390/pathogens11121554"]}}