Stimulated trans-acting factor of 50 kDa (Staf50) inhibits HIV-1 replication in human monocyte-derived macrophages

Bouazzaoui, Abdellatif; Kreutz, Marina; Eisert, Veronika; Dinauer, Norbert; Heinzelmann, Anna; Hallenberger, Sabine; Strayle, Jochen; Walker, Russel; Rübsamen‐Waigmann, Helga; Andreesen, Reinhard; Briesen, Hagen von

doi:10.1016/j.virol.2006.07.025

Cited by 60 publications

(62 citation statements)

References 49 publications

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“…We also demonstrated that TRIM22 was a RING finger E3 ubiquitin ligase (4), and its E3 ligase activity was responsible for its antiviral activity against encephalomycocarditis virus as reported by another research group (14). Additionally, several studies indicated that TRIM22 possessed antiretroviral activity depending on certain cell types (15)(16)(17).…”

supporting

confidence: 73%

A 5′ Extended IFN-Stimulating Response Element Is Crucial for IFN-γ–Induced Tripartite Motif 22 Expression via Interaction with IFN Regulatory Factor-1

Gao

Wang

et al. 2010

The Journal of Immunology

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Interferon-γ is crucial for the noncytopathic clearance of hepatitis B virus. In our previous study, we demonstrated that an IFN-γ–inducible molecule, tripartite motif (TRIM) 22, played an important role in antiviral immunity against hepatitis B virus. However, the molecular mechanism of TRIM22 induction by IFN-γ is still unclear. In this study, we identified a novel cis-element termed 5′ extended IFN-stimulating response element (5′ eISRE) that was crucial for IFN-γ inducibility of TRIM22 through transfection assays with luciferase reporter constructs and EMSAs. The 5′ eISRE consists of an ISRE-like motif (ACTTTCGTTTCTC) and a 6-bp sequence (AATTTA) upstream of it, and all three thymine triplets of this cis-element (AATTTAACTTTCGTTTCTC) were revealed to contribute to the IFN-γ inducibility of TRIM22 by site-directed mutagenesis. Further studies showed that upon IFN-γ stimulation, the 5′ eISRE could be bound by IFN regulatory factor-1 (IRF-1), but not by STAT1, as demonstrated by supershift analysis and an ELISA-based transcription factor assay. Moreover, overexpression of IRF-1 significantly induced TRIM22 expression, whereas silencing of IRF-1 with specific short interference RNA abolished IFN-γ–induced TRIM22 expression in HepG2 cells, indicating an IRF-1–dependent expression of TRIM22. Taken together, it was demonstrated in this study that a novel cis-element, 5′ eISRE, was crucial for the IFN-γ–induced transcriptional activity of the TRIM22 gene via interaction with IRF-1.

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supporting

confidence: 73%

A 5′ Extended IFN-Stimulating Response Element Is Crucial for IFN-γ–Induced Tripartite Motif 22 Expression via Interaction with IFN Regulatory Factor-1

Gao

Wang

et al. 2010

The Journal of Immunology

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“…TRIM22 has been shown to interfere with HIV-1 infection by either LTR promoter repression (Tissot & Mechti, 1995), inhibition of viral replication (Bouazzaoui et al, 2006) or reduction of particle production (Barr et al, 2008). Interestingly, the C-terminal SPRY domain of TRIM proteins is proposed to be involved in protein-protein interactions and RNA binding (Hilton et al, 1998;Ponting et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

“…TRIM22 (also known as Staf50) was first identified to be an IFN-induced human protein that represses transcription directed by the long terminal repeat (LTR) promoter region of human immunodeficiency virus type 1 (HIV-1) (Tissot & Mechti, 1995). Recently, TRIM22 has been reported to be a natural antiviral effector of both HIV-1 replication and particle production (Barr et al, 2008;Bouazzaoui et al, 2006). The effect of TRIM22 was abolished by mutation of amino acids Cys15 and Cys18 of its RING-finger domain, suggesting that functional ubiquitin ligase activity is required for TRIM22-mediated antiviral activities.…”

mentioning

confidence: 99%

TRIM22 E3 ubiquitin ligase activity is required to mediate antiviral activity against encephalomyocarditis virus

Eldin

Papon

Oteiza

et al. 2009

Journal of General Virology

110

108

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The interferon (IFN) system is a major effector of the innate immunity that allows time for the subsequent establishment of an adaptive immune response against a wide-range of pathogens. Their diverse biological actions are thought to be mediated by the products of specific but usually overlapping sets of cellular genes induced in the target cells. Ubiquitin ligase members of the tripartite motif (TRIM) protein family have emerged as IFN-induced proteins involved in both innate and adaptive immunity. In this report, we provide evidence that TRIM22 is a functional E3 ubiquitin ligase that is also ubiquitinated itself. We demonstrate that TRIM22 expression leads to a viral protection of HeLa cells against encephalomyocarditis virus infections. This effect is dependent upon its E3 ubiquitinating activity, since no antiviral effect was observed in cells expressing a TRIM22-deletion mutant defective in ubiquitinating activity. Consistent with this, TRIM22 interacts with the viral 3C protease (3C PRO ) and mediates its ubiquitination. Altogether, our findings demonstrate that TRIM22 E3 ubiquitin ligase activity represents a new antiviral pathway induced by IFN against picornaviruses. INTRODUCTIONPicornaviruses include important human pathogens such as rhinovirus, poliovirus and hepatitis A virus, as well as significant insect, plant and agricultural pathogens, such as foot-and-mouth disease virus (Whitton et al., 2005). Encephalomyocarditis virus (EMCV) is the prototype of the cardiovirus subgroup of picornaviruses. Its genome consists of a single-strand of messenger-sense RNA. Viral proteins are expressed from a large open reading frame encoding a giant precursor polyprotein (approx. 255 kDa), which is processed through a series of proteolytic cleavages to produce both capsid and non-structural proteins (Palmenberg, 1990). The majority of the processing reactions are carried out by the 3C protease (3C PRO ), which acts both inter-and intramolecularly to produce polyprotein precursors as well as the mature 3C PRO polypeptide (Palmenberg et al., 1979). Cleavage of the polyprotein normally occurs between glutamine-glycine or glutamine-serine amino acid pairs, which are usually flanked by proline residues (Palmenberg et al., 1984). Besides its commitment to the processing of the viral polyprotein, picornaviral 3C PRO can also facilitate virus replication by altering fundamental cellular processes such as transcription and translation of host cell mRNA (Barral et al., 2007;Ehrenfeld, 1982;Kuyumcu-Martinez et al., 2004; Neznanov et al., 2005;Shen et al., 1996;Yalamanchili et al., 1996Yalamanchili et al., , 1997. Because the regulated proteolysis mediated by 3C PRO is a critical feature in both the processing of picornaviral polyprotein and the inhibition of cellular defences, 3C PRO constitutes an important target for host antiviral innate pathways. Consistent with this, the degradation of EMCV 3C PRO by the ubiquitin/26S proteasome system has been reported (Losick et al., 2003;Schlax et al., 2007). Although the precise ro...

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“…For example, overexpression of TRIM22 can repress the transcription initiated by the long terminal repeat (LTR) promoter of human immunodeficiency virus (HIV) type-1 and inhibit HIV-1 replication in human monocyte-derived macrophages. 15,16 Recently it was reported that TRIM22 was the key mediator for type I IFN to inhibit HIV-1 replication. 10 Additionally, TRIM22 has been implicated in normal hematopoietic differentiation and in diseases such as systemic lupus erythematosus and Wilms tumor.…”

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confidence: 99%

Tripartite motif‐containing 22 inhibits the activity of hepatitis B virus core promoter, which is dependent on nuclear‐located RING domain†

et al. 2009

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Members of the tripartite motif (TRIM) family are a part of the innate immune system to counter intracellular pathogens. TRIM22 has been reported to possess antiretroviral activity. Here we report that TRIM22 is involved in antiviral immunity against hepatitis B virus (HBV). Our results showed that TRIM22, being a strongly induced gene by interferons in human hepatoma HepG2 cells, could inhibit HBV gene expression and replication in a cell culture system as well as in a mouse model system. Importantly, it was found that TRIM22 could inhibit the activity of HBV core promoter (CP) in a dose-dependent manner. However, TRIM22 lacking the C terminal SPRY domain lost this activity. Further study showed that the SPRY domain deletion mutant was localized exclusively to the cytoplasm of HepG2 cells. In contrast, the wild-type TRIM22 was localized to the nucleus, as expected for a transcriptional suppressor. Interestingly, although RING domain mutants of TRIM22 were localized to the nucleus, they could not inhibit HBV CP activity, indicating that TRIM22-mediated anti-HBV activity was dependent on the nuclear-located RING domain. W ith over 300 million carriers, hepatitis B virus (HBV) infection remains a major public health problem worldwide. 1 Classified in the Hepadnaviridae family, HBV is a small, enveloped DNA virus with a genome size of 3.2 kb. HBV replicates its partially double-stranded DNA genome within core particles by reverse transcription of encapsulated 3.5-kb pregenomic RNA (pgRNA), and thus is related to retroviruses. 2 The core promoter (CP) is responsible for the synthesis of pgRNA, and therefore the regulation of this promoter is important in the viral life cycle. It is well established that resolution of HBV infection is critically dependent on adaptive immunity, especially on HBVspecific cytotoxic T lymphocytes response. However, many studies also indicate that an innate immune response is crucial for early clearance of HBV infection. 3 For example, activation of Toll-like receptor signaling can inhibit HBV replication in vivo, and overexpression of an innate antiviral molecule, APOBEC3G, has also been shown to interfere with HBV replication efficiently. 4,5 Recent studies show that many members of the tripartite motif (TRIM) superfamily are expressed in response to interferons (IFNs) and display antiviral properties, targeting retroviruses in particular. 6,7 TRIM5␣, TRIM19, TRIM22, and TRIM28 were all demonstrated to play important roles in antiretroviral activities. [8][9][10][11][12] It has been speculated that the TRIM proteins may represent a new and widespread class of antiviral molecules involved in innate immunity. 6,7 The TRIM family is characterized by a combination of RING, B-Box, and coiled-coil domains, followed by one of several C-terminal domains. 13 To date, nearly 70 TRIM family members have been identified, yet the most intensively studied TRIM protein may be

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Stimulated trans-acting factor of 50 kDa (Staf50) inhibits HIV-1 replication in human monocyte-derived macrophages

Cited by 60 publications

References 49 publications

A 5′ Extended IFN-Stimulating Response Element Is Crucial for IFN-γ–Induced Tripartite Motif 22 Expression via Interaction with IFN Regulatory Factor-1

A 5′ Extended IFN-Stimulating Response Element Is Crucial for IFN-γ–Induced Tripartite Motif 22 Expression via Interaction with IFN Regulatory Factor-1

TRIM22 E3 ubiquitin ligase activity is required to mediate antiviral activity against encephalomyocarditis virus

Tripartite motif‐containing 22 inhibits the activity of hepatitis B virus core promoter, which is dependent on nuclear‐located RING domain†

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