The herpesviral antagonist m152 reveals differential activation of STING-dependent IRF and NF-κB signaling and STING's dual role during MCMV infection
| Autor: | Stempel, Markus, Chan, Baca, Juranić Lisnić, Vanda, Krmpotić, Astrid, Hartung, Josephine, Paludan, Søren R., Füllbrunn, Nadia, Lemmermann, Niels A.W., Brinkmann, Melanie M. |
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| Přispěvatelé: | HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
NF-B
INNATE ADAPTER Virus Replication NF-κB KAPPA-B ACTIVATION PATHWAY Mice DNA SENSOR herpesvirus Animals innate immunity IMMUNE EVASION PROTEINS Mice Knockout MURINE CYTOMEGALOVIRUS Mice Inbred BALB C Interferon Regulatory Factors/genetics NF-kappa B/genetics NF‐κB Membrane Proteins/physiology Membrane Glycoproteins/genetics IRF3 eye diseases Mice Inbred C57BL Cytomegalovirus Infections/immunology Host-Pathogen Interactions/immunology Interferon Type I/metabolism ANTIVIRAL DEFENSE Viral Proteins/genetics T-CELLS VIRUS Muromegalovirus/genetics Protein Binding STING |
| Zdroj: | The EMBO journal Stempel, M, Chan, B, Juranić Lisnić, V, Krmpotić, A, Hartung, J, Paludan, S R, Füllbrunn, N, Lemmermann, N A W & Brinkmann, M M 2019, ' The herpesviral antagonist m152 reveals differential activation of STING-dependent IRF and NF-κB signaling and STING's dual role during MCMV infection ', EMBO Journal, vol. 38, no. 5, e100983 . https://doi.org/10.15252/embj.2018100983 |
| DOI: | 10.15252/embj.2018100983 |
| Popis: | Cytomegaloviruses (CMVs) are master manipulators of the host immune response. Here, we reveal that the murine CMV (MCMV) protein m152 specifically targets the type I interferon (IFN) response by binding to stimulator of interferon genes (STING), thereby delaying its trafficking to the Golgi compartment from where STING initiates type I IFN signaling. Infection with an MCMV lacking m152 induced elevated type I IFN responses and this leads to reduced viral transcript levels both in vitro and in vivo. This effect is ameliorated in the absence of STING. Interestingly, while m152 inhibits STING-mediated IRF signaling, it did not affect STING-mediated NF-κB signaling. Analysis of how m152 targets STING translocation reveals that STING activates NF-κB signaling already from the ER prior to its trafficking to the Golgi. Strikingly, this response is important to promote early MCMV replication. Our results show that MCMV has evolved a mechanism to specifically antagonize the STING-mediated antiviral IFN response, while preserving its pro-viral NF-κB response, providing an advantage in the establishment of an infection. |
| Databáze: | OpenAIRE |
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