MPXV infection activates cGAS-STING signaling and IFN-I treatment reduces pathogenicity of mpox in CAST/EiJ mice and rhesus macaques.

ABSTRACT: The recent mpox outbreak underscores the urgent need for more accessible vaccines and treatments. However, the mpox virus (MPXV) clade IIb exhibits milder virulence and fails to develop typical pathological characteristics in mouse models. Herein, we found that CAST/EiJ mice infected intraperitoneally with MPXV clade IIb exhibited more efficient viral replication and experienced splenomegaly. Additionally, MPXV infection triggers the phosphorylation of stimulator of interferon genes (STING), TANK-binding kinase 1 (TBK1), and interferon regulatory factor 3 (IRF3) in ex vivo bone marrow-derived macrophages from mice and promotes the transcription of interferon (IFN)-β via the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-STING pathway. Notably, IFN-β treatment signif

SUBMITTER: Zhu L 

PROVIDER: S-EPMC12147887 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature