期刊
EMBO JOURNAL
卷 38, 期 5, 页码 -出版社
WILEY
DOI: 10.15252/embj.2018100983
关键词
herpesvirus; innate immunity; IRF3; NF-B; STING
资金
- Ministry of Science and Culture (MWK) of Lower Saxony, Germany
- Helmholtz Gemeinschaft, Virtual Institute VISTRIE [VH-VI-424]
- Deutsche Forschungsgemeinschaft [SFB 1292, BR3432/3-1TP11]
- European Regional Development Fund
- grant Strengthening the capacity of the Scientific Centre of Excellence CerVirVac for research in viral immunology and vaccinology [KK.01.1.1.01.0006]
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 invitro and invivo. This effect is ameliorated in the absence of STING. Interestingly, while m152 inhibits STING-mediated IRF signaling, it did not affect STING-mediated NF-B signaling. Analysis of how m152 targets STING translocation reveals that STING activates NF-B 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-B response, providing an advantage in the establishment of an infection.
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