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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.

Show MeSH
Human TRIM proteins.Classification of human TRIM proteins based on the nature of their C-terminal domains(s) as defined by Short and Cox [54] and modified by Ozato et al. [3]. The TRIM protein family is composed of 11 sub-families, from C-I to C-XI, whereas some TRIM proteins remain unclassified (UC), since they do not have a RING finger domain as “true” TRIM proteins. NHL, NHL repeats; COS, COS box motif; FN3, fibronectin type III motif; PHD, plant homeodomain; BROMO, bromodomain; MATH, meprin and TRAF homology domain; TM, transmembrane domain; AR, acid-rich region.
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pone-0004894-g001: Human TRIM proteins.Classification of human TRIM proteins based on the nature of their C-terminal domains(s) as defined by Short and Cox [54] and modified by Ozato et al. [3]. The TRIM protein family is composed of 11 sub-families, from C-I to C-XI, whereas some TRIM proteins remain unclassified (UC), since they do not have a RING finger domain as “true” TRIM proteins. NHL, NHL repeats; COS, COS box motif; FN3, fibronectin type III motif; PHD, plant homeodomain; BROMO, bromodomain; MATH, meprin and TRAF homology domain; TM, transmembrane domain; AR, acid-rich region.

Mentions: 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]. Interestingly, an increasing number of TRIM proteins have been found to display antiviral activities or are known to be involved in processes associated with innate immunity [2], [3]. TRIM5α is responsible for a species-specific post-entry restriction of diverse retroviruses, including N-MLV and HIV-1, in primate cells [4], [5], [6], [7], [8], whereas TRIM1/MID2 also displays an anti-retroviral activity which affects specifically N-MLV infection [8]. TRIM22, also known as Staf50, has been shown to inhibit HIV-1 replication, although it is still unclear at what step the block occurs [9], [10], [11]. TRIM28 restricts MLV LTR-driven transcription in murine embryonic cells [12]. Furthermore, the inhibition of a wide range of RNA and DNA viruses by TRIM19/PML has been reported [13]. The most extensive screen performed to date showed that several TRIM proteins, including TRIM11, TRIM31 and TRIM62, can interfere with various stages of MLV or HIV-1 replication [14]. Finally, TRIM25 has been shown to control RIG-I-mediated antiviral activity through its E3 ubiquitin ligase activity [15].


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)

Human TRIM proteins.Classification of human TRIM proteins based on the nature of their C-terminal domains(s) as defined by Short and Cox [54] and modified by Ozato et al. [3]. The TRIM protein family is composed of 11 sub-families, from C-I to C-XI, whereas some TRIM proteins remain unclassified (UC), since they do not have a RING finger domain as “true” TRIM proteins. NHL, NHL repeats; COS, COS box motif; FN3, fibronectin type III motif; PHD, plant homeodomain; BROMO, bromodomain; MATH, meprin and TRAF homology domain; TM, transmembrane domain; AR, acid-rich region.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2654144&req=5

pone-0004894-g001: Human TRIM proteins.Classification of human TRIM proteins based on the nature of their C-terminal domains(s) as defined by Short and Cox [54] and modified by Ozato et al. [3]. The TRIM protein family is composed of 11 sub-families, from C-I to C-XI, whereas some TRIM proteins remain unclassified (UC), since they do not have a RING finger domain as “true” TRIM proteins. NHL, NHL repeats; COS, COS box motif; FN3, fibronectin type III motif; PHD, plant homeodomain; BROMO, bromodomain; MATH, meprin and TRAF homology domain; TM, transmembrane domain; AR, acid-rich region.
Mentions: 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]. Interestingly, an increasing number of TRIM proteins have been found to display antiviral activities or are known to be involved in processes associated with innate immunity [2], [3]. TRIM5α is responsible for a species-specific post-entry restriction of diverse retroviruses, including N-MLV and HIV-1, in primate cells [4], [5], [6], [7], [8], whereas TRIM1/MID2 also displays an anti-retroviral activity which affects specifically N-MLV infection [8]. TRIM22, also known as Staf50, has been shown to inhibit HIV-1 replication, although it is still unclear at what step the block occurs [9], [10], [11]. TRIM28 restricts MLV LTR-driven transcription in murine embryonic cells [12]. Furthermore, the inhibition of a wide range of RNA and DNA viruses by TRIM19/PML has been reported [13]. The most extensive screen performed to date showed that several TRIM proteins, including TRIM11, TRIM31 and TRIM62, can interfere with various stages of MLV or HIV-1 replication [14]. Finally, TRIM25 has been shown to control RIG-I-mediated antiviral activity through its E3 ubiquitin ligase activity [15].

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