PPM1G restricts innate immune signaling mediated by STING and MAVS and is hijacked by KSHV for immune evasion

Abstract

dependent 1G (PPM1G) as a negative regulator of innate immune pathways and showed that this host system is hijacked by Kaposi's sarcoma-associated herpesvirus (KSHV). Mechanistically, KSHV tegument protein ORF33 interacts with STING/MAVS and enhances recruitment of PPM1G to dephosphorylate p-STING/p-MAVS for immunosuppression. Inhibition of PPM1G expression improves the antiviral response against both DNA and RNA viruses. Collectively, our study shows that PPM1G restricts both cytosolic DNA- and RNA-sensing pathways to naturally balance the intensity of the antiviral response. Manipulation of PPM1G by KSHV provides an important strategy for immune evasion.

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