RNA Virus hijacks TRIM29 to suppress the host innate immune response

Abstract

Abstract The host response to RNA virus infection relies on an intrinsic innate immune response to restrict viral replication. Antiviral signaling activation of innate immunity requires strict modulation to avoid damage to the host from exacerbated cytokines and inflammation. However, the precise mechanism of how antiviral signaling activation is strictly controlled still remains obscure. Here, we found the E3 ligase TRIM29 was specifically expressed in poly I:C induced human myeloid dendritic cells (mDCs). TRIM29 was highly induced in human mDCs in response to poly I:C and played negative role to type I interferon (IFN) production. The deficiency in TRIM29 resulted in enhanced type I interferon responses to poly I:C and reovirus infection. Importantly, challenge of wildtype mice with reovirus led to lethal infection. In contrast, deletion of TRIM29 protected the mice from this developing lethality. Additionally, the heart, intestine, spleen, liver and brain of TRIM29−/− mice exhibited attenuated viral loads of reovirus. Meanwhile, the heart of TRIM29−/− mice showed elevated type I IFN production. Mechanistically, TRIM29 was shown to interact with MAVS, the key adaptor in the RNA sensing pathway, and induce its ubiquitination and degradation. Taken together, RNA virus hijacks the E3 ligase TRIM29 to shut down the host innate immune response for immune evasion.