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

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Sarute , N , Ibrahim , N , Fagla , B M , Lavanya , M , Cuevas , C , Stavrou , S , Otkiran-Clare , G , Tyynismaa , H , Henao-Mejia , J & Ross , S R 2019 , ' TRIM2, a novel member of the antiviral family, limits New World arenavirus entry ' , PLoS Biology , vol. 17 , no. 2 , 3000137 . https://doi.org/10.1371/journal.pbio.3000137

Title: TRIM2, a novel member of the antiviral family, limits New World arenavirus entry
Author: Sarute, Nicolas; Ibrahim, Nouhou; Fagla, Bani Medegan; Lavanya, Madakasira; Cuevas, Christian; Stavrou, Spyridon; Otkiran-Clare, Guliz; Tyynismaa, Henna; Henao-Mejia, Jorge; Ross, Susan R.
Contributor: University of Helsinki, STEMM - Stem Cells and Metabolism Research Program
Date: 2019-02
Language: eng
Number of pages: 26
Belongs to series: PLoS Biology
ISSN: 1544-9173
URI: http://hdl.handle.net/10138/300437
Abstract: 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 Junin 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 alpha (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.
Subject: UBIQUITIN LIGASE TRIM2
TRANSFERRIN RECEPTOR 1
PROTEOME-SCALE MAP
JUNIN VIRUS
I INTERFERON
CELL ENTRY
IDENTIFICATION
BINDING
MOTIF
CD47
3111 Biomedicine
1182 Biochemistry, cell and molecular biology
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