TRIM41-Mediated Ubiquitination of Nucleoprotein Limits Vesicular Stomatitis Virus Infection

Patil, Girish; Xu, Lingling; Wu, Yunqin; Song, Kun; Hao, Wenzhuo; Fang, Hua; Wang, Lingyan; Li, Shitao

doi:10.3390/v12020131

Cited by 26 publications

(20 citation statements)

References 38 publications

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“…We repeated those experiments with a TRIM41 RING domain mutant lacking the E3 ubiquitin ligase activity (deletion of amino acids 16–60; ΔRING-TRIM41) ( Figure S5D ; Lassot et al, 2018 ; Patil et al, 2020 ). Transfection of WT-TRIM41 lowered R338W-TOP3Bccs, whereas transfection of the ΔRING-TRIM41 failed to decrease TOP3Bccs ( Figures S5E and S5F ).…”

Section: Resultsmentioning

confidence: 99%

DNA and RNA Cleavage Complexes and Repair Pathway for TOP3B RNA- and DNA-Protein Crosslinks

et al. 2020

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SUMMARY The present study demonstrates that topoisomerase 3B (TOP3B) forms both RNA and DNA cleavage complexes (TOP3Bccs) in vivo and reveals a pathway for repairing TOP3Bccs. For inducing and detecting cellular TOP3Bccs, we engineer a “self-trapping” mutant of TOP3B (R338W-TOP3B). Transfection with R338W-TOP3B induces R-loops, genomic damage, and growth defect, which highlights the importance of TOP3Bcc repair mechanisms. To determine how cells repair TOP3Bccs, we deplete tyrosyl-DNA phosphodiesterases (TDP1 and TDP2). TDP2-deficient cells show elevated TOP3Bccs both in DNA and RNA. Conversely, overexpression of TDP2 lowers cellular TOP3Bccs. Using recombinant human TDP2, we demonstrate that TDP2 can process both denatured and proteolyzed TOP3Bccs. We also show that cellular TOP3Bccs are ubiquitinated by the E3 ligase TRIM41 before undergoing proteasomal processing and excision by TDP2.

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Section: Resultsmentioning

confidence: 99%

DNA and RNA Cleavage Complexes and Repair Pathway for TOP3B RNA- and DNA-Protein Crosslinks

et al. 2020

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“…TRIM14 and TRIM22 have been reported to promote IAV nucleoprotein (NP) ubiquitination, and degradation in a proteasome-dependent manner [44,45]. Viral NPs are attractive candidates as TRIM targets as TRIM41 also recognizes vesicular stomatitis virus (VSV) NP suggesting this system of TRIM redundancy or "cross-talk" may be applicable to other viruses [46]. The strategy of degrading viral RNA-binding proteins in order to reveal its genome for host detection is a common theme amongst several TRIMs.…”

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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“…There are also some intrinsic host restriction factors that are constitutively expressed, they also have antiviral effects. These "preexisted" host factors response more quickly and directly inhibit virus replication [50].For example, TRIM41 impeds In uenza A virus and some RNA virus infection via K48-mediated ubiquitination which lead to protein degradation [8,51]. Here, we report that pOASL participates in MDA5-mediated IFN signal pathway.…”

Section: Discussionmentioning

confidence: 73%

Interferon Inducible Porcine 2′, 5′-oligoadenylate Synthetase-Like Protein Limits Porcine Reproductive and Respiratory Syndrome Virus Infection via the MDA5-Mediated Interferon-Signaling Pathway

Zhao¹,

Kong²,

Kang³

et al. 2020

Preprint

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Porcine reproductive and respiratory syndrome virus (PRRSV) is a constant threat to the swine industry worldwide. Currently approved vaccines against PRRSV are losing effectiveness, as new viral strains are often refractory to conventional treatments. Thus, there is an urgent need to find new therapeutic targets to develop novel antiviral drugs. 2′, 5′-oligoadenylate synthetase-like (OASL) protein has antiviral activity, but this has not been demonstrated for PRRSV and the mechanism is not well elucidated. In this study expression of porcine OASL (pOASL) in porcine alveolar macrophages (PAMs) induced by interferon (IFN) -β stimulation and PRRSV infection was examined by real-time polymerase chain reaction (RT-PCR). Exogenous expression and knockdown of pOASL were used to indicate the role of pOASL in the PRRSV replication cycle. The type I IFN signaling pathway was evaluated after pOASL overexpression. Results showed the expression of pOASL in PAMs was significantly increased by IFN-β stimulation or PRRSV infection. pOASL specific small interfering RNA (siRNA) promoted PRRSV replication, whereas exogenous expression of pOASL inhibited infection of PRRSV. The anti-PRRSV activity was lost after knockdown of the Melanoma differentiation-associated protein 5 (MDA5) RNA sensor. Taken together, pOASL inhibits PRRSV infection via the activation of MDA5.

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TRIM41-Mediated Ubiquitination of Nucleoprotein Limits Vesicular Stomatitis Virus Infection

Cited by 26 publications

References 38 publications

DNA and RNA Cleavage Complexes and Repair Pathway for TOP3B RNA- and DNA-Protein Crosslinks

DNA and RNA Cleavage Complexes and Repair Pathway for TOP3B RNA- and DNA-Protein Crosslinks

TRIM Proteins in Host Defense and Viral Pathogenesis

Interferon Inducible Porcine 2′, 5′-oligoadenylate Synthetase-Like Protein Limits Porcine Reproductive and Respiratory Syndrome Virus Infection via the MDA5-Mediated Interferon-Signaling Pathway

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