The herpesviral antagonist m152 reveals differential activation of STING-dependent IRF and NF-κB signaling and STING's dual role during MCMV infection.
EMBO J
; 38(5)2019 03 01.
Article
em En
| MEDLINE
| ID: mdl-30696688
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas Virais
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Glicoproteínas de Membrana
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Interferon Tipo I
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NF-kappa B
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Infecções por Citomegalovirus
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Fatores Reguladores de Interferon
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Interações Hospedeiro-Patógeno
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Proteínas de Membrana
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article