TRIM2, a novel member of the antiviral family, limits New World arenavirus entry

by Nicolas Sarute, Nouhou Ibrahim, Bani Medegan Fagla, Madakasira Lavanya, Christian Cuevas, Spyridon Stavrou, Guliz Otkiran-Clare, Henna Tyynismaa, Jorge Henao-Mejia, Susan R. Ross

Tripartite motif (TRIM) proteins belong to a large family with many roles in host biology, including restricting virus infection. Here, we found that TRIM2, which has been implicated in cases of Charcot–Marie–Tooth disease (CMTD) in humans, acts by blocking hemorrhagic fever New World arenavirus (NWA) entry into cells. We show that Trim2-knockout mice, as well as primary fibroblasts from a CMTD patient with mutations in TRIM2, are more highly infected by the NWAs Junín and Tacaribe virus than wild-type mice or cells are. Using mice with different Trim2 gene deletions and TRIM2 mutant constructs, we demonstrate that its antiviral activity is uniquely independent of the RING domain encoding ubiquitin ligase activity. Finally, we show that one member of the TRIM2 interactome, signal regulatory protein α (SIRPA), a known inhibitor of phagocytosis, also restricts NWA infection and conversely that TRIM2 limits phagocytosis of apoptotic cells. In addition to demonstrating a novel antiviral mechanism for TRIM proteins, these studies suggest that the NWA entry and phagocytosis pathways overlap.

Source link

Related posts

Spying on Arctic peregrine falcons


Plan U: Universal access to scientific and medical research via funder preprint mandates


Cross-linker-mediated regulation of actin network organization controls tissue morphogenesis


This website uses cookies to improve your experience. We'll assume you're ok with this, but you can opt-out if you wish. Accept Read More

Privacy & Cookies Policy