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Human TRIM gene expression in response to interferons.

Carthagena L, Bergamaschi A, Luna JM, David A, Uchil PD, Margottin-Goguet F, Mothes W, Hazan U, Transy C, Pancino G, Nisole S - PLoS ONE (2009)

Bottom Line: 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.Our 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.

View Article: PubMed Central - PubMed

Affiliation: Département des Maladies Infectieuses, Institut Cochin, Université Paris Descartes, CNRS, UMR 8104, Paris, France.

ABSTRACT

Background: Tripartite motif (TRIM) proteins constitute a family of proteins that share a conserved tripartite architecture. The recent discovery of the anti-HIV activity of TRIM5alpha in primate cells has stimulated much interest in the potential role of TRIM proteins in antiviral activities and innate immunity.

Principal findings: To 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 FcgammaR-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 FcgammaR-activated macrophages.

Conclusions: Our 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.

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Phylogenetic tree of human TRIM proteins.This joining-neighbor-tree of human TRIM proteins deleted from their Ct domain(s) was constructed using the CLUSTALW and NJplot programs. Numbers indicate bootstrap proportions after 1000 replications. The scale bar represents 0.05 substitutions per amino acid position. Red boxes show TRIM genes which are up-regulated by type I IFN in macrophages, whereas blue boxes show TRIM genes which are up-regulated following activation of MDM with immune complex (IC). TRIM genes belonging to the 11p15.4 cluster are indicated.
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pone-0004894-g006: Phylogenetic tree of human TRIM proteins.This joining-neighbor-tree of human TRIM proteins deleted from their Ct domain(s) was constructed using the CLUSTALW and NJplot programs. Numbers indicate bootstrap proportions after 1000 replications. The scale bar represents 0.05 substitutions per amino acid position. Red boxes show TRIM genes which are up-regulated by type I IFN in macrophages, whereas blue boxes show TRIM genes which are up-regulated following activation of MDM with immune complex (IC). TRIM genes belonging to the 11p15.4 cluster are indicated.

Mentions: There appears to be no correlation between the susceptibility to IFNs and the domain structure. Indeed, TRIM5, 6, 21, 22, 25, 26, 34, 35, 38, 58 and 69 present the RBCC/B30.2 structure characteristic of the C-IV TRIM subfamily, according to the Short and Cox classification [54] (Figure 1), whereas TRIM19/PML, TRIM31 and 56 belong to the C-V subfamily and TRIM14 and TRIM20/MEFV have not been sub-classified, since they lack the RING domain [54] (Figure 1). As shown in Figure 6, TRIM genes whose expression is up-regulated by type I IFN are dispersed throughout the phylogenetic tree of human TRIM genes. The only correlation concerns the TRIM genes localized in the 11p15.4 cluster, which comprise TRIM5, 6, 22 and 34, all of them being up-regulated by IFNs (Figure 6), an observation that has also been reported in murine cells [35]. Two other IFN-induced TRIM genes, TRIM26 (induced by both type I and II IFNs) and TRIM31 (only induced by type I IFN) are located within another major cluster of TRIM encoding genes (containing TRIM10, 15, 26, 31, 39 and 40) located in the major histocompatibility complex region on chromosome 6, at 6p21.33 [55].


Human TRIM gene expression in response to interferons.

Carthagena L, Bergamaschi A, Luna JM, David A, Uchil PD, Margottin-Goguet F, Mothes W, Hazan U, Transy C, Pancino G, Nisole S - PLoS ONE (2009)

Phylogenetic tree of human TRIM proteins.This joining-neighbor-tree of human TRIM proteins deleted from their Ct domain(s) was constructed using the CLUSTALW and NJplot programs. Numbers indicate bootstrap proportions after 1000 replications. The scale bar represents 0.05 substitutions per amino acid position. Red boxes show TRIM genes which are up-regulated by type I IFN in macrophages, whereas blue boxes show TRIM genes which are up-regulated following activation of MDM with immune complex (IC). TRIM genes belonging to the 11p15.4 cluster are indicated.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2654144&req=5

pone-0004894-g006: Phylogenetic tree of human TRIM proteins.This joining-neighbor-tree of human TRIM proteins deleted from their Ct domain(s) was constructed using the CLUSTALW and NJplot programs. Numbers indicate bootstrap proportions after 1000 replications. The scale bar represents 0.05 substitutions per amino acid position. Red boxes show TRIM genes which are up-regulated by type I IFN in macrophages, whereas blue boxes show TRIM genes which are up-regulated following activation of MDM with immune complex (IC). TRIM genes belonging to the 11p15.4 cluster are indicated.
Mentions: There appears to be no correlation between the susceptibility to IFNs and the domain structure. Indeed, TRIM5, 6, 21, 22, 25, 26, 34, 35, 38, 58 and 69 present the RBCC/B30.2 structure characteristic of the C-IV TRIM subfamily, according to the Short and Cox classification [54] (Figure 1), whereas TRIM19/PML, TRIM31 and 56 belong to the C-V subfamily and TRIM14 and TRIM20/MEFV have not been sub-classified, since they lack the RING domain [54] (Figure 1). As shown in Figure 6, TRIM genes whose expression is up-regulated by type I IFN are dispersed throughout the phylogenetic tree of human TRIM genes. The only correlation concerns the TRIM genes localized in the 11p15.4 cluster, which comprise TRIM5, 6, 22 and 34, all of them being up-regulated by IFNs (Figure 6), an observation that has also been reported in murine cells [35]. Two other IFN-induced TRIM genes, TRIM26 (induced by both type I and II IFNs) and TRIM31 (only induced by type I IFN) are located within another major cluster of TRIM encoding genes (containing TRIM10, 15, 26, 31, 39 and 40) located in the major histocompatibility complex region on chromosome 6, at 6p21.33 [55].

Bottom Line: 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.Our 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.

View Article: PubMed Central - PubMed

Affiliation: Département des Maladies Infectieuses, Institut Cochin, Université Paris Descartes, CNRS, UMR 8104, Paris, France.

ABSTRACT

Background: Tripartite motif (TRIM) proteins constitute a family of proteins that share a conserved tripartite architecture. The recent discovery of the anti-HIV activity of TRIM5alpha in primate cells has stimulated much interest in the potential role of TRIM proteins in antiviral activities and innate immunity.

Principal findings: To 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 FcgammaR-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 FcgammaR-activated macrophages.

Conclusions: Our 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.

Show MeSH