Publication Date:
2019
Description:
〈p〉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 〈i〉in vitro〈/i〉 and 〈i〉in vivo〈/i〉. 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.〈/p〉
Print ISSN:
0261-4189
Electronic ISSN:
1460-2075
Topics:
Biology
,
Medicine
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