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The herpesviral antagonist m152 reveals differential activation of STING ‐dependent IRF and NF ‐κB signaling and STING 's dual role during MCMV infection
Author(s) -
Stempel Markus,
Chan Baca,
Juranić Lisnić Vanda,
Krmpotić Astrid,
Hartung Josephine,
Paludan Søren R,
Füllbrunn Nadia,
Lemmermann Niels AW,
Brinkmann Melanie M
Publication year - 2019
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2018100983
Subject(s) - biology , sting , microbiology and biotechnology , signal transduction , cytosol , antagonist , receptor , biochemistry , enzyme , aerospace engineering , engineering
Cytomegaloviruses ( CMV s) 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.