Sera from Trypanosoma b. gambiense infected patients cross-react with a Trypanosoma cruzi recombinant protein

In previous studies, we and others have shown utility of a 24-kDa #Trypanosoma cruzi recombinant antigen (rTc24) for serological diagnosis of Chagas' disease. Also, this molecule has been proved useful to evaluate cure of chagasic patients who submit to specific treatment. However, in all the studies done so far, the 24-kDa protein was used as a fusion with a Gluthatione-S-transferase (GST) of #Schistosoma japonicum, therefore, parallel assays to determine the anti-GST responses of all sera were required to deduce the GST noise in serological tests. Here, we show the subcloning by polymerase chain reaction of the cDNA encoding the #T. cruzi$ 24-kDa antigen in a vector system (pQE) allowing us to obtain Tc24 recombinant protein as a single molecule. The highly reactivity of chagasic sera from Colombia, Ecuador, Brazil and Bolivia in ELISA against the recombinant antigen is confirmed. However, sera from patients infected with African trypanosomes recognize rTc24 in ELISA and blot. The relevance of these findings in the context of Chagas' disease diagnosis and/or the relationship with African trypanosomes is analyzed. (Résumé d'auteur

Antiviral TRIMs: friend or foe in autoimmune and autoinflammatory disease?

The concept that viral sensing systems, via their ability to drive pro-inflammatory cytokine and interferon production, contribute to the development of autoimmune and autoinflammatory disease is supported by a wide range of clinical and experimental observations. Recently, the tripartite motif-containing proteins (TRIMs) have emerged as having key roles in antiviral immunity — either as viral restriction factors or as regulators of pathways downstream of viral RNA and DNA sensors, and the inflammasome. Given their involvement in these pathways, we propose that TRIM proteins contribute to the development and pathology of autoimmune and autoinflammatory conditions, thus making them potential novel targets for therapeutic manipulation

Exportin-5-mediated nuclear export of eukaryotic elongation factor 1A and tRNA

Transport of proteins and RNA into and out of the cell nucleus is mediated largely by a family of RanGTP-binding transport receptors. Export receptors (exportins) need to bind RanGTP for efficient loading of their export cargo. We have identified eukaryotic elongation factor 1A (eEF1A) and tRNA as RanGTP-dependent binding partners of exportin-5 (Exp5). Exp5 stimulates nuclear export of eEF1A when microinjected into the nucleus of Xenopus laevis oocytes. Surprisingly, the interaction between eEF1A and Exp5 is dependent on tRNA that can interact directly with Exp5 and, if aminoacylated, recruits eEF1A into the export complex. These data suggested to us that Exp5 might support tRNA export. Indeed, not only the canonical tRNA export receptor, exportin-t, but also Exp5 can drive nuclear export of tRNA. Taken together, we show that there exists an alternative tRNA export pathway which can be exploited to keep eEF1A out of the cell nucleus

TRIM68 negatively regulates IFN-β production by degrading TRK fused gene, a novel driver of IFN-β downstream of anti-viral detection systems.

In recent years members of the tripartite motif-containing (TRIM) family of E3 ubiquitin ligases have been shown to both positively and negatively regulate viral defence and as such are emerging as compelling targets for modulating the anti-viral immune response. In this study we identify TRIM68, a close homologue of TRIM21, as a novel regulator of Toll-like receptor (TLR)- and RIG-I-like receptor (RLR)-driven type I IFN production. Proteomic analysis of TRIM68-containing complexes identified TRK-fused gene (TFG) as a potential TRIM68 target. Overexpression of TRIM68 and TFG confirmed their ability to associate, with TLR3 stimulation appearing to enhance the interaction. TFG is a known activator of NF-κB via its ability to interact with inhibitor of NF-κB kinase subunit gamma (IKK-γ) and TRAF family member-associated NF-κB activator (TANK). Our data identifies a novel role for TFG as a positive regulator of type I IFN production and suggests that TRIM68 targets TFG for lysosomal degradation, thus turning off TFG-mediated IFN-β production. Knockdown of TRIM68 in primary human monocytes resulted in enhanced levels of type I IFN and TFG following poly(I:C) treatment. Thus TRIM68 targets TFG, a novel regulator of IFN production, and in doing so turns off and limits type I IFN production in response to anti-viral detection systems