Naslov
The herpesviral antagonist m152 reveals differential activation of STING-dependent IRF and NF-kappa 2B signaling and STING's dual role during MCMV infection

Autori
Stempel, Markus ; Chan, Baca ; Lisnic, Vanda Juranic ; Krmpotic, Astrid ; Hartung, Josephine ; Paludan, Soren R. ; Fuellbrunn, Nadia ; Lemmermann, Niels A. W. ; Brinkmann, Melanie M.

Izvornik
EMBO journal (0261-4189) 38 (2019), 5; 100983, 26

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
herpesvirus ; innate immunity ; IRF3 ; NF-B ; STING

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA