Macrophage expressed TRIM47 is required to control RNA virus infection by targeting MAVS

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Presentation Time: 01:15 PM - 01:30 PM
Abstract ID: 4194 - A

Presenting Author:
Wenting Lu , Postdoctoral Fellow at Houston Methodist Academic Inst.

Abstract:

In the past half century, there have been multiple RNA virus pandemics (influenza 1957, 1968 and 2009; SARS-CoV and COVID-19), inhabiting 44% of all emerging contagious diseases. Innate immunity is the first line of defense against viral infection. Here we found that TRIM47, a member of the TRIM family E3 ligase, plays a pivotal role in positively regulating host innate immunity in response to Influenza A virus (IAV). Among immune cells, TRIM47 is highly expressed in macrophages. Compared with wild type, TRIM47 deficient bone marrow derived macrophages exhibited a significantly lower level of type I interferon (IFN-I) following RNA mimics infection, encompassing IAV and poly I: C. After in vivo IAV infection, TRIM47 knockout mice showed an extremely lower survival rate, along with a lower level of IFN-I, higher viral load and more inflammatory cell infiltration in lungs compared to wild-type mice. Mechanistically, TRIM47 induces K68-linked ubiquitination of mitochondrial antiviral-signaling protein (MAVS), a key adaptor in RNA-sensing pathway, leading to robust IFN-I production. This K68-linked ubiquitination by TRIM47 is essential for MAVS aggregation and activation in macrophage. These findings provide compelling evidence that TRIM47 interacts with MAVS, enhancing IFN-I production to effectively restrict IAV infection in macrophages. This research not only advances our understanding of influenza pathogenesis but also opens avenues for potential therapeutic interventions.