Human TRIM Gene Expression in Response to Interferons

Laetitia Carthagena,Anna Bergamaschi,Sébastien Nisole,Joseph M Luna,Pradeep D Uchil,Annie David,Walther Mothes,Florence Margottin-Goguet,Gianfranco Pancino,Uriel Hazan,Catherine Transy

doi:10.1371/journal.pone.0004894

Abstract

BackgroundTripartite motif (TRIM) proteins constitute a family of proteins that share a conserved tripartite architecture. The recent discovery of the anti-HIV activity of TRIM5α in primate cells has stimulated much interest in the potential role of TRIM proteins in antiviral activities and innate immunity.Principal FindingsTo test if TRIM genes are up-regulated during antiviral immune responses, we performed a systematic analysis of TRIM gene expression in human primary lymphocytes and monocyte-derived macrophages in response to interferons (IFNs, type I and II) or following FcγR-mediated activation of macrophages. We found that 27 of the 72 human TRIM genes are sensitive to IFN. Our analysis identifies 9 additional TRIM genes that are up-regulated by IFNs, among which only 3 have previously been found to display an antiviral activity. Also, we found 2 TRIM proteins, TRIM9 and 54, to be specifically up-regulated in FcγR-activated macrophages.ConclusionsOur results present the first comprehensive TRIM gene expression analysis in primary human immune cells, and suggest the involvement of additional TRIM proteins in regulating host antiviral activities.

Highlights

Tripartite motif (TRIM) proteins constitute a protein family based on a conserved domain architecture that is characterized by a RING finger domain, one or two B-box domains, a Coiled-coil domain and a variable C-terminus [1] (Figure 1)
We have shown that the aggregation of FccR by immune complexes (IC) inhibits replication of HIV-1 and related lentiviruses in human monocyte-derived macrophages [39,40]
In order to perform a comprehensive study of TRIM gene expression in human primary lymphocytes and macrophages, unstimulated peripheral blood lymphocytes (PBL) and monocyte derived macrophages (MDM) from 3 donors were either left untreated or stimulated with type I IFN, type II IFN or immune complexes (IC, in the case of Monocyte derived macrophages (MDM) only), as indicated in the Materials and Methods section

Summary

Introduction

Tripartite motif (TRIM) proteins constitute a protein family based on a conserved domain architecture (known as RBCC) that is characterized by a RING finger domain, one or two B-box domains, a Coiled-coil domain and a variable C-terminus [1] (Figure 1). Despite their common domain architecture, TRIM proteins are implicated in a variety of cellular functions, including differentiation, apoptosis and immunity [1]. The recent discovery of the anti-HIV activity of TRIM5a in primate cells has stimulated much interest in the potential role of TRIM proteins in antiviral activities and innate immunity

Methods

Results

Conclusion