Vesicular Stomatitis Virus Transcription Is Inhibited by TRIM69 in the Interferon-Induced Antiviral State

Kueck, Tonya; Bloyet, Louis-Marie; Cassella, Elena; Zang, Trinity; Schmidt, Fabian; Brusic, Vesna; Tekes, Gergely; Pornillos, Owen; Whelan, Sean P. J.; Bieniasz, Paul D.

doi:10.1128/jvi.01372-19

Cited by 27 publications

(30 citation statements)

References 42 publications

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“…Multimerization has been shown to be important for the antiviral activity of TRIM69, with the L99R mutation inhibiting filament and cytoplasmic body formation (Kueck et al, 2019). In our structure, this residue is located within the fourhelical bundle that forms the majority of the dimer interface.…”

Section: Structure Of the Trim69 Ring Domainmentioning

confidence: 83%

“…As has been shown previously for other TRIM proteins, the removal of hydrophobic residues from or the insertion of charged residues into the four-helix bundle is also sufficient to inhibit dimerization. The L99R mutation used here was sufficient to inhibit assembly; interestingly, a similar mutation, L99A, has recently been used to remove the TRIM69-mediated block to VSIV infection (Kueck et al, 2019).…”

Section: Characteristics Of Trim Ring-domain Dimerizationmentioning

confidence: 95%

“…Recent studies have suggested that the multimerization of TRIM69 is important for antiviral activity (Kueck et al, 2019;Rihn et al, 2019). Based on the conserved N-terminal domain architecture of TRIM69 (Fig.…”

Section: The Oligomeric State Of Trim69 N-terminal Domainsmentioning

confidence: 99%

“…Recently, two independent studies have identified TRIM69 as an inhibitor of Vesicular stomatitis Indiana virus (VSIV; previously known as Vesicular stomatitis virus, VSV; Kueck et al, 2019;Rihn et al, 2019). It was found that multimerization was required for this antiviral activity.…”

Section: Introductionmentioning

confidence: 99%

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The RING domain of TRIM69 promotes higher-order assembly

Keown

Yang

Black

et al. 2020

Acta Cryst Sect D Struct Biol

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Members of the TRIM protein family have been shown to inhibit a range of viral infections. Recently, TRIM69 was identified as a potent inhibitor of Vesicular stomatitis Indiana virus infection, with its inhibition being dependent upon multimerization. Using SEC-MALLS analysis, it is demonstrated that the assembly of TRIM69 is mediated through the RING domain and not the Bbox domain as has been shown for other TRIM proteins. Using X-ray crystallography, the structure of the TRIM69 RING domain has been determined to a resolution of 2.1 Å, the oligomerization interface has been identified and regions outside the four-helix bundle have been observed to form interactions that are likely to support assembly.

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Section: Structure Of the Trim69 Ring Domainmentioning

confidence: 83%

Section: Characteristics Of Trim Ring-domain Dimerizationmentioning

confidence: 95%

Section: The Oligomeric State Of Trim69 N-terminal Domainsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The RING domain of TRIM69 promotes higher-order assembly

Keown

Yang

Black

et al. 2020

Acta Cryst Sect D Struct Biol

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“…The autoantibodies we identified against TRIM proteins, other than TRIM33 and TRIM21, have not been observed previously in IIM. TRIM69 inhibits vesicular stomatitis virus transcription and interacts with dengue virus non-structural protein 3 to mediate its poly-ubiquitination and degradation (Kueck et al, 2019;Wang et al, 2018). TRIMs also regulate antiviral pathways indirectly by mediating innate immunity, influencing the transcription of TI-IFNs, pro-inflammatory cytokines and interferon-stimulated genes (van Tol et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Microbial and autoantibody immunogenic repertoires in TIF1γ autoantibody positive dermatomyositis

Megremis

Walker

et al. 2020

Preprint

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We investigate the accumulated microbial and autoantigen antibody repertoire in adult-onset dermatomyositis patients sero-positive for TIF1γ (TRIM33) autoantibodies. We use an untargeted high-throughput approach which combines immunoglobulin disease-specific epitope-enrichment and identification of microbial and human antigens. Increased microbial diversity was observed in dermatomyositis. Viruses were over-represented and species of the Poxviridae family were significantly enriched. The autoantibodies identified recognised a large portion of the human proteome, including interferon regulated proteins; these proteins were clustered in specific biological processes. Apart from TRIM33, autoantibodies against eleven further TRIM proteins, including TRIM21, were identified. Some of these TRIM proteins shared epitope homology with specific viral species including poxviruses. Our data suggest antibody accumulation in dermatomyositis against an expanded diversity of microbial and human proteins and evidence of non-random targeting of specific signalling pathways. Our findings indicate that molecular mimicry and epitope spreading events may play a significant role in the pathogenesis of dermatomyositis.

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TRIM Proteins in Host Defense and Viral Pathogenesis

Giraldo

Hage

Tol

et al. 2020

Curr Clin Micro Rpt

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Purpose of Review Tripartite motif (TRIM) proteins are a large group of E3 ubiquitin ligases involved in different cellular functions. Of special interest are their roles in innate immunity, inflammation, and virus replication. We discuss novel roles of TRIM proteins during virus infections that lead to increased pathogenicity. Recent Findings TRIM proteins regulate different antiviral and inflammatory signaling pathways, mostly by promoting ubiquitination of important factors including pattern recognition receptors, adaptor proteins, kinases, and transcription factors that are involved in type I interferon and NF-κB pathways. Therefore, viruses have developed mechanisms to target TRIMs for immune evasion. New evidence is emerging indicating that viruses have the ability to directly use TRIMs and the ubiquitination process to enhance the viral replication cycle and cause increased pathogenesis. A new report on TRIM7 also highlights the potential pro-viral role of TRIMs via ubiquitination of viral proteins and suggests a novel mechanism by which ubiquitination of virus envelope protein may provide determinants of tissue and species tropism. Summary TRIM proteins have important functions in promoting host defense against virus infection; however, viruses have adapted to evade TRIM-mediated immune responses and can hijack TRIMs to ultimately increase virus pathogenesis. Only by understanding specific TRIM-virus interactions and by using more in vivo approaches can we learn how to harness TRIM function to develop therapeutic approaches to reduce virus pathogenesis.

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Vesicular Stomatitis Virus Transcription Is Inhibited by TRIM69 in the Interferon-Induced Antiviral State

Cited by 27 publications

References 42 publications

The RING domain of TRIM69 promotes higher-order assembly

The RING domain of TRIM69 promotes higher-order assembly

Microbial and autoantibody immunogenic repertoires in TIF1γ autoantibody positive dermatomyositis

TRIM Proteins in Host Defense and Viral Pathogenesis

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