Interferon alpha (IFNα)-induced TRIM22 interrupts HCV replication by ubiquitinating NS5A

Yang, Chunxu; Zhao, Xinhao; Sun, Dakang; Yang, Leilei; Chang, Chong E.; Pan, Yu; Chi, Xiumei; Gao, Yanhang; Wang, Moli; Shi, Xiaodong; Sun, Haibo; Lv, Juan; Gao, Yuanda; Zhong, Jin; Niu, Junqi; Sun, Bing

doi:10.1038/cmi.2014.131

Cited by 77 publications

(80 citation statements)

References 35 publications

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“…TRIM14 and TRIM22 are two TRIMs that function as ISGs during hepatitis C virus (HCV) infection [78,79]. The presence of either TRIM14 or TRIM22 conferred restriction against HCV replication that depended on an interaction with the viral NS5A protein in both cases [78,79]. This interaction resulted in the destruction of the viral NS5A by ubiquitination and subsequent proteasome targeting [78,79].…”

Section: Proteasome-dependent Antiviral Mechanismsmentioning

confidence: 99%

“…The presence of either TRIM14 or TRIM22 conferred restriction against HCV replication that depended on an interaction with the viral NS5A protein in both cases [78,79]. This interaction resulted in the destruction of the viral NS5A by ubiquitination and subsequent proteasome targeting [78,79]. Although TRIM14 is known to function as a mitochondrial adaptor for IFN and NF-κB signalling, usage of the TRIM14 mutant that fails to mediate innate immune signalling (K365R) revealed restriction against HCV was unaltered [78].…”

Section: Proteasome-dependent Antiviral Mechanismsmentioning

confidence: 99%

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To TRIM or not to TRIM: the balance of host–virus interactions mediated by the ubiquitin system

Hage

Rajsbaum

2019

Journal of General Virology

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The innate immune system responds rapidly to protect against viral infections, but an overactive response can cause harmful damage. To avoid this, the response is tightly regulated by post-translational modifications (PTMs). The ubiquitin system represents a powerful PTM machinery that allows for the reversible linkage of ubiquitin to activate and deactivate a target's function. A precise enzymatic cascade of ubiquitin-activating, conjugating and ligating enzymes facilitates ubiquitination. Viruses have evolved to take advantage of the ubiquitin pathway either by targeting factors to dampen the antiviral response or by hijacking the system to enhance their replication. The tripartite motif (TRIM) family of E3 ubiquitin ligases has garnered attention as a major contributor to innate immunity. Many TRIM family members limit viruses either indirectly as components in innate immune signalling, or directly by targeting viral proteins for degradation. In spite of this, TRIMs and other ubiquitin ligases can be appropriated by viruses and repurposed as valuable tools in viral replication. This duality of function suggests a new frontier of research for TRIMs and raises new challenges for discerning the subtleties of these pro-viral mechanisms. Here, we review current findings regarding the involvement of TRIMs in host-virus interactions. We examine ongoing developments in the field, including novel roles for unanchored ubiquitin in innate immunity, the direct involvement of ubiquitin ligases in promoting viral replication, recent controversies on the role of ubiquitin and TRIM25 in activation of the pattern recognition receptor RIG-I, and we discuss the implications these studies have on future research directions.

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Section: Proteasome-dependent Antiviral Mechanismsmentioning

confidence: 99%

Section: Proteasome-dependent Antiviral Mechanismsmentioning

confidence: 99%

To TRIM or not to TRIM: the balance of host–virus interactions mediated by the ubiquitin system

Hage

Rajsbaum

2019

Journal of General Virology

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“…TRIM22 inhibits the transcription and replication of HIV‐1 via blocking the long terminal repeats and disrupting intracellular transport of GAG protein (Barr et al, ). In addition, TRIM22 is also proven to be resistant to Influenza A virus by targeting the viral nucleoprotein for degradation (Di et al, ), Hepatitis C (HCV) by ubiquitinating NS5A (Yang et al, ), HBV through its single CpG methylation (Lim et al, ). These findings reveal an important role of TRIM22 as a RF in intrinsic antiviral immunity.…”

Section: Introductionmentioning

confidence: 99%

TRIM22 knockdown suppresses chronic myeloid leukemia via inhibiting PI3K/Akt/mTOR signaling pathway

Li-yin

et al. 2018

Cell Biology International

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Tripartite motif-containing 22 (TRIM22) is reported to participate in numerous cellular activities. Recent studies confirm that TRIM22 is a target gene for P53, and inhibits clonogenic growth of leukemic U-937 cells. The current study aims to discover the effect of TRIM22 in progression of human chronic myeloid leukemia (CML) and explore the related mechanism. TRIM22 was knocked down by siRNA transfection in CML cell K562. We observed that TRIM22 knockdown decreased proliferation and invasion in K562 cells. TRIM22 knockdown significantly induced cell cycle arrest by regulating the level of CDK4, Cyclin D1, P70S6K, and P53 in K562 cell. Moreover, loss of TRIM22 also promoted apoptosis through modulation of Bcl-2, Bax and active Caspase 3 in K562 cell. Furthermore, we demonstrated that TRIM22 knockdown inhibited the activation of PI3K/Akt/mTOR pathway by decreasing the level of the phosphorylated form p-Akt and p-mTOR in K562 cell. In conclusion, loss of TRIM22 suppresses the progression and invasion of CML through regulation of PI3K/Akt/mTOR pathway, suggesting that TRIM22 might be as a potential target for the treatment strategy of CML.

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“…36,37 First, we tested the effects of Rubicon overexpression and knockdown on cell viability. Our results demonstrated that neither condition significantly influenced the growth of Huh7 cells (data not shown).…”

Section: Rubicon Affects the Expression Of Ifns And Ifn Downstream Efmentioning

confidence: 99%

Inducible Rubicon facilitates viral replication by antagonizing interferon production

et al. 2017

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The RUN domain Beclin-1-interacting cysteine-rich-containing (Rubicon) protein is involved in the maturation step of autophagy and the endocytic pathway as a Beclin-1-binding partner, but little is known regarding the role of Rubicon during viral infection. Here, we performed functional studies of the identified target in interferon (IFN) signaling pathways associated with Rubicon to elucidate the mechanisms of viral resistance to IFN. The Rubicon protein levels were elevated in peripheral blood mononuclear cells, sera and liver tissues from patients with hepatitis B virus (HBV) infection relative to those in healthy individuals. Assays of the overexpression and knockdown of Rubicon showed that Rubicon significantly promoted HBV replication. In addition, Rubicon knockdown resulted in the inhibition of enterovirus 71, influenza A virus and vesicular stomatitis virus. The expression o0f Rubicon led to the suppression of virus-induced type-I interferon (IFN-α and IFN-β) and type-III interferon (IFN-λ1). Translocation of activated IRF3 and IRF7 from the cytoplasm to the nucleus was involved in this process, and the NF-κB essential modulator (NEMO), a key factor in the IFN pathway, was the target with which Rubicon interacted. Our results reveal a previously unrecognized function of Rubicon as a virus-induced protein that binds to NEMO, leading to the inhibition of type-I interferon production. Rubicon thus functions as an important negative regulator of the innate immune response, enhances viral replication and may play a role in viral immune evasion.

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Interferon alpha (IFNα)-induced TRIM22 interrupts HCV replication by ubiquitinating NS5A

Cited by 77 publications

References 35 publications

To TRIM or not to TRIM: the balance of host–virus interactions mediated by the ubiquitin system

To TRIM or not to TRIM: the balance of host–virus interactions mediated by the ubiquitin system

TRIM22 knockdown suppresses chronic myeloid leukemia via inhibiting PI3K/Akt/mTOR signaling pathway

Inducible Rubicon facilitates viral replication by antagonizing interferon production

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