TRIM29 suppresses the innate immune response to RNA virus

Abstract The innate immunity is critically important in protection against virus infections, and in the case of RNA viral infections, the signaling mechanisms that initiate robust protective innate immunity without triggering autoimmune inflammation remain incompletely defined. We have previously found that TRIM29 is constitutively expressed in alveolar macrophages and plays a critical role in the control of innate immunity in respiratory tract. Also, we have shown that TRIM29 is highly expressed in human airway epithelial cells and promotes DNA virus infections by inhibiting innate immune response. Here, we found the E3 ligase TRIM29 was specifically expressed in poly I:C stimulated human myeloid dendritic cells (mDCs). The induced TRIM29 played a negative role in type I interferon (IFN) production in response to poly I:C or dsRNA virus reovirus infection. Importantly, the challenge of wildtype mice with reovirus led to lethal infection. In contrast, deletion of TRIM29 protected the mice from this developing lethality. Additionally, TRIM29−/− mice have lower titers of reovirus in the heart, intestine, spleen, liver, and brain due to elevated production of type I IFN. Mechanistically, TRIM29 was shown to interact with MAVS and subsequently induce its K11-linked ubiquitination and degradation. Taken together, TRIM29 regulates negatively the host innate immune response to RNA virus, which could be employed by RNA viruses for immune evasion.