TRIM E3 Ligases Interfere with Early and Late Stages of the Retroviral Life Cycle

Uchil, Pradeep D.; Quinlan, Brian D.; Chan, Wai-Tsing; Luna, Joseph M.; Mothes, Walther

doi:10.1371/journal.ppat.0040016

Cited by 213 publications

(213 citation statements)

References 42 publications

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“…Previous studies have shown that many TRIM proteins are induced in response to interferons and that TRIM proteins are important components of resistance to pathogens and are involved in many biological processes [20]. TRIM5 is involved in pathogen recognition and regulation of transcriptional pathways in host defense.…”

Section: Discussionmentioning

confidence: 99%

TRIM59 interacts with ECSIT and negatively regulates NF-κB and IRF-3/7-mediated signal pathways

Kondo

Watanabe

Hatakeyama

2012

Biochemical and Biophysical Research Communications

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Innate immune responses are triggered by pathogen-associated molecular patterns (PAMPs) through pattern recognition receptors (PRRs) and then activate intracellular signaling pathways including NF-B and interferon regulatory factors. Recently, it has been reported that tripartite motif (TRIM) proteins function as crucial regulators via ubiquitin-mediated modifications for these signaling pathways. In this study, we showed that one of the TRIM family ubiquitin ligases, TRIM59, interacts with ECSIT as an adaptor protein required for the TLR-mediated transduction pathway. Luciferase reporter assays using reporter plasmids including NF-B responsive element, interferon (IFN-) promoter and interferon-sensitive response element (ISRE) showed that overexpression of TRIM59 repressed their transcriptional activities, whereas knockdown of TRIM59 enhanced their transcriptional activities. Furthermore, TRIM59 inhibited phosphorylation and dimerization of IRF3 and IRF7, suggesting that TRIM59 negatively regulates upstream kinases for IRFs. These findings indicate that TRIM59 may serve as a multifunctional regulator for innate immune signaling pathways.3

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Section: Discussionmentioning

confidence: 99%

TRIM59 interacts with ECSIT and negatively regulates NF-κB and IRF-3/7-mediated signal pathways

Kondo

Watanabe

Hatakeyama

2012

Biochemical and Biophysical Research Communications

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“…With respect to a role for TRIMs as viral restriction factors there has been an explosion of information in recent years [8,46,47]. In particular, a study by Uchil et al [47] in which they screened various human and mouse TRIMs, demonstrated that TRIMs act nearly every stage in viral replication (summarised in table 2).…”

Section: Trims As Viral Restriction Factors and Potential Link With Amentioning

confidence: 99%

“…In particular, a study by Uchil et al [47] in which they screened various human and mouse TRIMs, demonstrated that TRIMs act nearly every stage in viral replication (summarised in table 2). This section aims to provide an update on emerging TRIMs in this area and potential links with autoimmunity.…”

Section: Trims As Viral Restriction Factors and Potential Link With Amentioning

confidence: 99%

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

2011

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“…Because the TRIM5␣ coiled-coil domain controls protein oligomerization (3,6,9,11), this observation implies that the multimerization of TRIM5␣rh is not necessary for the encapsidation and that a TRIM5␣rh monomer interacts with HIV-1 Gag polyproteins during the late restriction. We note with interest the recent observation that TRIM15 can block retroviral production (31). Similar to the TRIM5␣rh-mediated late restriction, TRIM15 does not require the B30.2(PRYSPRY) or coiled-coil domains of TRIM15 to interact with the murine leukemia virus Gag in the producer cells (31).…”

Section: Discussionmentioning

confidence: 85%

“…We note with interest the recent observation that TRIM15 can block retroviral production (31). Similar to the TRIM5␣rh-mediated late restriction, TRIM15 does not require the B30.2(PRYSPRY) or coiled-coil domains of TRIM15 to interact with the murine leukemia virus Gag in the producer cells (31). Thus, recognition of retroviral Gag proteins without forming multimers may be a universal property among TRIM family proteins that affect the late phase of retroviral life cycles.…”

Section: Discussionmentioning

confidence: 89%

Determinants for the Rhesus Monkey TRIM5α-mediated Block of the Late Phase of HIV-1 Replication

Sakuma

Ohmine

Ikeda

2010

Journal of Biological Chemistry

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Rhesus monkey TRIM5␣ (TRIM5␣rh) includes RING, B-box, coiled-coil, and B30.2(PRYSPRY) domains and blocks HIV-1 infection by targeting HIV-1 core through a B30.2(PRYSPRY) domain. Previously, we reported that TRIM5␣rh also blocks HIV-1 production in a B30.2(PRYSPRY)-independent manner. Efficient encapsidation of TRIM5␣rh, but not human TRIM5␣ (TRIM5␣hu), in HIV-1 virus-like particles suggests the interaction between Gag and TRIM5␣rh during viral assembly. Here, we determined responsible regions for late restriction activity of TRIM5␣rh. The RING disruption, but not the replacement with human TRIM21 RING, ablated the efficient encapsidation and the late restriction, suggesting that a RING structure was essential for the late restriction and efficient interaction with HIV-1 Gag. The prominent cytoplasmic body formation of TRIM5␣rh, which depended on the coiled-coil domain and the ensuing linker 2 region, was not required for the encapsidation. Intriguingly, TRIM5␣rh coiled-coil domain mutants (M133T and/or T146A) showed impaired late restriction activity, despite the efficient encapsidation and cytoplasmic body formation. Our results suggest that the TRIM5␣rh-mediated late restriction involves at least two distinct activities as follows: (i) interaction with HIV-1 Gag polyprotein through the N-terminal, RING, and B-box 2 regions of a TRIM5␣rh monomer, and (ii) an effector function(s) that depends upon the coiled-coil and linker 2 domains of TRIM5␣rh. We speculate that the TRIM5␣rh coiledcoil region recruits additional factor(s), such as other TRIM family proteins or a cellular protease, during the late restriction. RBCC domains of TRIM family proteins may play a role in sensing newly synthesized viral proteins as a part of innate immunity against viral infection.

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TRIM E3 Ligases Interfere with Early and Late Stages of the Retroviral Life Cycle

Cited by 213 publications

References 42 publications

TRIM59 interacts with ECSIT and negatively regulates NF-κB and IRF-3/7-mediated signal pathways

TRIM59 interacts with ECSIT and negatively regulates NF-κB and IRF-3/7-mediated signal pathways

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

Determinants for the Rhesus Monkey TRIM5α-mediated Block of the Late Phase of HIV-1 Replication

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