The herpesviral antagonist m152 reveals differential activation of STING-dependent IRF and NF-?B signaling and STING's dual role during MCMV infection.

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-?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.

SUBMITTER: Stempel M 

PROVIDER: S-EPMC6396373 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature