The E3 Ubiquitin Ligase TRIM21 Promotes HBV DNA Polymerase Degradation

Mu, Ting; Zhao, Xiaoqing; Zhu, Yanan; Fan, Hongxia; Tang, Hua

doi:10.3390/v12030346

Cited by 44 publications

(40 citation statements)

References 66 publications

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“…TRIM21 promotes the destruction of viral capsids via the proteasome and exposes the viral DNA or RNA to cytosolic nucleic acid sensors like cGAS and RIG-I [47]. In addition to NP, the polymerase complexes of viruses are subject to this means of disposal as TRIM32 targets the influenza polymerase subunit PB1 of several IAV strains to the proteasome via ubiquitination, while TRIM21 interacts with the hepatitis B virus (HBD) DNA polymerase to achieve the same effect for ubiquitination and proteasomal degradation [48,49].…”

Section: Antiviral Activity Of Trim Proteinsmentioning

confidence: 99%

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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Section: Antiviral Activity Of Trim Proteinsmentioning

confidence: 99%

TRIM Proteins in Host Defense and Viral Pathogenesis

Giraldo

Hage

Tol

et al. 2020

Curr Clin Micro Rpt

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show abstract

“…TRIM21 was originally identified as an autoantigen in autoimmune diseases, including rheumatoid arthritis, Systemic lupus erythematosus, and Sjogren’s syndrome ( Schulte-Pelkum et al, 2009 ). TRIM21 acts as an important factor involved in the innate immune responses against microbial infection, including bacterial, viral, and parasite ( Hos et al, 2020 ; Mu et al, 2020 ; Xie et al, 2020 ), however, little about TRIM21 is known for parasites infection. In this study, we reported that T. gondii RH and CEP infection upregulated the expression of TRIM21, thus restricted parasite replication through NF-κB activation.…”

Section: Discussionmentioning

confidence: 99%

Toxoplasma gondii Type-I ROP18 Targeting Human E3 Ligase TRIM21 for Immune Escape

Yao

Zhou

et al. 2021

Front. Cell Dev. Biol.

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Toxoplasma gondii is an intracellular pathogen that exerts its virulence through inhibiting host’s innate immune responses, which is mainly related to the type II interferon (IFN-γ) response. IFN-γ inducible tripartite motif 21 (TRIM21), an E3 ligase, plays an important role in anti-infection responses against the intracellular pathogens including bacteria, virus, and parasite. We found that T. gondii virulence factor ROP18 of the type I RH strain (TgROP18I) interacted with human TRIM21, and promoted the latter’s phosphorylation, which subsequently accelerated TRIM21 degradation through lysosomal pathway. Furthermore, TRIM21 protein level was found to be upregulated during RH and CEP strains of T. gondii infection. TRIM21 knocking down reduced the ubiquitin labeling on the parasitophorous vacuole membrane (PVM) [which led to parasitophorous vacuole (PV) acidification and death of CEP tachyzoites], and relieved the inhibition of CEP proliferation induced by IFN-γ in human foreskin fibroblast (HFF) cells which was consistent with the result of TRIM21 overexpression. On the other hand, TRIM21 overexpression enhanced the inhibition of CEP proliferation, and inhibited the binding of IκB-α with p65 to activate the IFN-γ-inducible NF-κB pathway, which might be resulted by TRIM21-IκB-α interaction. In brief, our research identified that in human cells, IFN-γ-inducible TRIM21 functioned in the innate immune responses against type III T. gondii infection; however, TgROP18I promoted TRIM21 phosphorylation, leading to TRIM21 degradation for immune escape in type I strain infection.

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“…TRIM25 targets CpG-rich sites in the genomes of Sindbis virus (SINV) and HIV-1, and inhibits translation of the incoming virus genome ( 61 , 62 ). TRIM21 suppresses hepatitis B virus (HBV) DNA replication by promoting the ubiquitination of HBV DNA polymerase ( 63 ). TRIM41 targets the viral nucleoprotein of vesicular stomatitis virus (VSV) for ubiquitination and subsequent protein degradation ( 64 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of a Shrimp E3 Ubiquitin Ligase TRIM50-Like Involved in Restricting White Spot Syndrome Virus Proliferation by Its Mediated Autophagy and Ubiquitination

et al. 2021

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Most tripartite motif (TRIM) family proteins are critical components of the autophagy machinery and play important roles in host defense against viral pathogens in mammals. However, the roles of TRIM proteins in autophagy and viral infection have not been studied in lower invertebrates, especially crustaceans. In this study, we first identified a TRIM50-like gene from Penaeus monodon (designated PmTRIM50-like), which, after a white spot syndrome virus (WSSV) challenge, was significantly upregulated at the mRNA and protein levels in the intestine and hemocytes. Knockdown of PmTRIM50-like led to an increase in the WSSV quantity in shrimp, while its overexpression led to a decrease compared with the controls. Autophagy can be induced by WSSV or rapamycin challenge and has been shown to play a positive role in restricting WSSV replication in P. monodon. The mRNA and protein expression levels of PmTRIM50-like significantly increased with the enhancement of rapamycin-induced autophagy. The autophagy activity induced by WSSV or rapamycin challenge could be inhibited by silencing PmTRIM50-like in shrimp. Further studies showed that rapamycin failed to induce autophagy or inhibit WSSV replication after knockdown of PmTRIM50-like. Moreover, pull-down and in vitro ubiquitination assays demonstrated that PmTRIM50-like could interact with WSSV envelope proteins and target them for ubiquitination in vitro. Collectively, this study demonstrated that PmTRIM50-like is required for autophagy and is involved in restricting the proliferation of WSSV through its ubiquitination. This is the first study to report the role of a TRIM family protein in virus infection and host autophagy in crustaceans.

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The E3 Ubiquitin Ligase TRIM21 Promotes HBV DNA Polymerase Degradation

Cited by 44 publications

References 66 publications

TRIM Proteins in Host Defense and Viral Pathogenesis

TRIM Proteins in Host Defense and Viral Pathogenesis

Toxoplasma gondii Type-I ROP18 Targeting Human E3 Ligase TRIM21 for Immune Escape

Identification of a Shrimp E3 Ubiquitin Ligase TRIM50-Like Involved in Restricting White Spot Syndrome Virus Proliferation by Its Mediated Autophagy and Ubiquitination

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