Type I Interferon Signaling Controls Gammaherpesvirus Latency In Vivo
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...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | Pathogens |
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| Online Access: | https://www.mdpi.com/2076-0817/11/12/1554 |
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| author | Johannes Schwerk Lucas Kemper Kendra A. Bussey Stefan Lienenklaus Siegfried Weiss Luka Čičin-Šain Andrea Kröger Ulrich Kalinke Christopher M. Collins Samuel H. Speck Martin Messerle Dagmar Wirth Melanie M. Brinkmann Hansjörg Hauser Mario Köster |
| author_facet | Johannes Schwerk Lucas Kemper Kendra A. Bussey Stefan Lienenklaus Siegfried Weiss Luka Čičin-Šain Andrea Kröger Ulrich Kalinke Christopher M. Collins Samuel H. Speck Martin Messerle Dagmar Wirth Melanie M. Brinkmann Hansjörg Hauser Mario Köster |
| author_sort | Johannes Schwerk |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T15:59:07Z |
| format | Article |
| id | doaj.art-2db1caf9db6a4ebcb475422ae96a09da |
| institution | Directory Open Access Journal |
| issn | 2076-0817 |
| language | English |
| last_indexed | 2024-03-09T15:59:07Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pathogens |
| spelling | doaj.art-2db1caf9db6a4ebcb475422ae96a09da2023-11-24T17:14:43ZengMDPI AGPathogens2076-08172022-12-011112155410.3390/pathogens11121554Type I Interferon Signaling Controls Gammaherpesvirus Latency In VivoJohannes Schwerk0Lucas Kemper1Kendra A. Bussey2Stefan Lienenklaus3Siegfried Weiss4Luka Čičin-Šain5Andrea Kröger6Ulrich Kalinke7Christopher M. Collins8Samuel H. Speck9Martin Messerle10Dagmar Wirth11Melanie M. Brinkmann12Hansjörg Hauser13Mario Köster14Model System for Infection and Immunity, Helmholtz Centre for Infection Research (HZI), 38124 Braunschweig, GermanyModel System for Infection and Immunity, Helmholtz Centre for Infection Research (HZI), 38124 Braunschweig, GermanyInstitute of Genetics, Technische Universität Braunschweig, 38106 Braunschweig, GermanyInstitute for Laboratory Animal Science, Hannover Medical School, 30625 Hannover, GermanyInstitute of Immunology, Hannover Medical School, 30625 Hannover, GermanyViral Immunology, Helmholtz Centre for Infection Research (HZI), 38124 Braunschweig, GermanyInnate Immunity and Infection, Helmholtz Centre for Infection Research (HZI), 38124 Braunschweig, GermanyInstitute for Experimental Infection Research, Twincore, 30625 Hannover, GermanyDepartment of Microbiology & Immunology, Emory University Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USADepartment of Microbiology & Immunology, Emory University Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USADepartment of Virology, Hannover Medical School, 30625 Hannover, GermanyModel System for Infection and Immunity, Helmholtz Centre for Infection Research (HZI), 38124 Braunschweig, GermanyInstitute of Genetics, Technische Universität Braunschweig, 38106 Braunschweig, GermanyModel System for Infection and Immunity, Helmholtz Centre for Infection Research (HZI), 38124 Braunschweig, GermanyModel System for Infection and Immunity, Helmholtz Centre for Infection Research (HZI), 38124 Braunschweig, GermanyGammaherpesviruses, 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.https://www.mdpi.com/2076-0817/11/12/1554murine gammaherpesvirus 68latencychronic infectiontype I interferon |
| spellingShingle | Johannes Schwerk Lucas Kemper Kendra A. Bussey Stefan Lienenklaus Siegfried Weiss Luka Čičin-Šain Andrea Kröger Ulrich Kalinke Christopher M. Collins Samuel H. Speck Martin Messerle Dagmar Wirth Melanie M. Brinkmann Hansjörg Hauser Mario Köster Type I Interferon Signaling Controls Gammaherpesvirus Latency In Vivo Pathogens murine gammaherpesvirus 68 latency chronic infection type I interferon |
| title | Type I Interferon Signaling Controls Gammaherpesvirus Latency In Vivo |
| title_full | Type I Interferon Signaling Controls Gammaherpesvirus Latency In Vivo |
| title_fullStr | Type I Interferon Signaling Controls Gammaherpesvirus Latency In Vivo |
| title_full_unstemmed | Type I Interferon Signaling Controls Gammaherpesvirus Latency In Vivo |
| title_short | Type I Interferon Signaling Controls Gammaherpesvirus Latency In Vivo |
| title_sort | type i interferon signaling controls gammaherpesvirus latency in vivo |
| topic | murine gammaherpesvirus 68 latency chronic infection type I interferon |
| url | https://www.mdpi.com/2076-0817/11/12/1554 |
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