The USP18 cysteine protease promotes HBV production independent of its protease activity

Li, Yujia; Yao, Ming; Duan, Xiaoqiong; Yé, Haiyan; Li, Shilin; Chen, Limin; Yang, Chunhui; Chen, Yongjun

doi:10.1186/s12985-020-01304-2

Cited by 7 publications

(6 citation statements)

References 39 publications

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“…-IFNα is without IFN-α treatment, and +IFNα is with IFN-α treatment. Data are presented as mean ± SD; Error bars indicate SD; **P < 0.01, ***P < 0.001. others and our laboratories showed that USP18 promotes HBV production by inhibiting the type I IFN signaling pathway (Li et al, 2016(Li et al, , 2020. Interestingly, it has been reported that cells developed IFN resistance following DENV infection.…”

Section: Discussionmentioning

confidence: 75%

“…Similar findings were reported in pre-treatment liver tissues of patients chronically infected with HBV ( Xiao et al, 2012 ). Previous work from others and our laboratories showed that USP18 promotes HBV production by inhibiting the type I IFN signaling pathway ( Li et al, 2016 , 2020 ).…”

Section: Discussionmentioning

confidence: 81%

“…Our study observed overexpression of USP18 significantly increased DENV-2 replication ( Figure 2 ), while knockdown of USP18 decreased DENV-2 replication ( Figure 3 ). Similarly, knockout or knockdown of USP18 in mice or cells exhibit increased antiviral activity against various viruses, including lymphocytic choriomeningitis virus (LCMV), vesicular stomatitis virus (VSV), Sindbis virus (SINV), Hepatitis B virus (HBV), and Human immunodeficiency virus 1 (HIV-1) ( Lenschow et al, 2005 ; Osiak et al, 2005 ; Kim et al, 2008 ; Taylor et al, 2018 ; Li et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

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USP18 Mediates Interferon Resistance of Dengue Virus Infection

et al. 2021

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Previous studies demonstrated that dengue virus (DENV) infection developed resistance to type-I interferons (IFNα/β). The underlying mechanism remains unclear. USP18 is a negative regulator of IFNα/β signaling, and its expression level is significantly increased following DENV infection in cell lines and patients’ blood. Our previous study revealed that increased USP18 expression contributed to the IFN-α resistance of Hepatitis C Virus (HCV). However, the role of USP18 in DENV replication and resistance to IFN-α is elusive. In this current study, we aimed to explore the role of USP18 in DENV-2 replication and resistance to IFN-α. The level of USP18 was up-regulated by plasmid transfection and down-regulated by siRNA transfection in Hela cells. USP18, IFN-α, IFN-β expression, and DENV-2 replication were monitored by qRT-PCR and Western blot. The activation of the Jak/STAT signaling pathway was assessed at three levels: p-STAT1/p-STAT2 (Western blot), interferon-stimulated response element (ISRE) activity (Dual-luciferase assay), and interferon-stimulated genes (ISGs) expression (qRT-PCR). Our data showed that DENV-2 infection increased USP18 expression in Hela cells. USP18 overexpression promoted DENV-2 replication, while USP18 silence inhibited DENV-2 replication. Silence of USP18 potentiated the anti-DENV-2 activity of IFN-α through activation of the IFN-α-mediated Jak/STAT signaling pathway as shown by increased expression of p-STAT1/p-STAT2, enhanced ISRE activity, and elevated expression of some ISGs. Our data indicated that USP18 induced by DENV-2 infection is a critical host factor utilized by DENV-2 to confer antagonism on IFN-α.

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Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

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USP18 Mediates Interferon Resistance of Dengue Virus Infection

et al. 2021

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“…Additionally, USP18 dampens the effects of type I and type III IFNs by exerting negative feedback control through its regulatory role (89). Moreover, USP18 also binds to and deubiquitinates TAK1, thereby promoting hepatic inflammatory responses (90)(91)(92).…”

Section: Viral Hepatitismentioning

confidence: 99%

Roles of ubiquitin-specific proteases in inflammatory diseases

Chen,

Zhang,

et al. 2024

Front. Immunol.

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Ubiquitin-specific proteases (USPs), as one of the deubiquitinating enzymes (DUBs) families, regulate the fate of proteins and signaling pathway transduction by removing ubiquitin chains from the target proteins. USPs are essential for the modulation of a variety of physiological processes, such as DNA repair, cell metabolism and differentiation, epigenetic modulations as well as protein stability. Recently, extensive research has demonstrated that USPs exert a significant impact on innate and adaptive immune reactions, metabolic syndromes, inflammatory disorders, and infection via post-translational modification processes. This review summarizes the important roles of the USPs in the onset and progression of inflammatory diseases, including periodontitis, pneumonia, atherosclerosis, inflammatory bowel disease, sepsis, hepatitis, diabetes, and obesity. Moreover, we highlight a comprehensive overview of the pathogenesis of USPs in these inflammatory diseases as well as post-translational modifications in the inflammatory responses and pave the way for future prospect of targeted therapies in these inflammatory diseases.

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“…ISGF3 translocates to the nucleus, where it binds to the ISRE and induces the expression of a few hundred ISGs to exert their antiviral or pro-viral activity. [6][7][8][9] The UMP-CMP kinase 2 (CMPK2) has recently been reported to be associated with virus infection and host antiviral response.…”

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confidence: 99%

UMP‐CMP kinase 2 inhibits ZIKV replication through activation of type I IFN signaling pathway

Zhu,

Tan,

Shi

et al. 2024

Journal of Medical Virology

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Cytidine/uridine monophosphate kinase 2 (UMP‐CMP kinase 2, CMPK2) has been reported as an antiviral interferon‐stimulated gene (ISG). We previously observed that the expression of CMPK2 was significantly upregulated after Zika Virus (ZIKV) infection in A549 cells. However, the association and the underlying mechanisms between CMPK2 induction and ZIKV replication remain to be determined. We investigated the induction of CMPK2 during ZIKV infection and the effect of CMPK2 on ZIKV replication in A549, U251, Vero, IFNAR‐deficient U5A and its parental 2fTGH cells, Huh7 and its RIG‐I‐deficient derivatives Huh7.5.1 cells. The activation status of Jak‐STAT signaling pathway was determined by detecting the phosphorylation level of STAT1, the activity of interferon stimulated response element (ISRE) and the expression of several interferon stimulated genes (ISGs). We found that ZIKV infection induced CMPK2 expression through an IFNAR and RIG‐I dependent manner. Overexpression of CMPK2 inhibited while CMPK2 knockdown promoted ZIKV replication in A549 and U251 cells. Mechanically, we found that CMPK2 overexpression increased IFNβ expression and activated Jak/STAT signaling pathway as shown by the increased level of p‐STAT1, enhanced activity of ISRE, and the upregulated expression of downstream ISGs. These findings suggest that ZIKV infection induced CMPK2 expression, which inhibited ZIKV replication and serves as a positive feedback regulator for IFN‐Jak/STAT pathway.

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The USP18 cysteine protease promotes HBV production independent of its protease activity

Cited by 7 publications

References 39 publications

USP18 Mediates Interferon Resistance of Dengue Virus Infection

USP18 Mediates Interferon Resistance of Dengue Virus Infection

Roles of ubiquitin-specific proteases in inflammatory diseases

UMP‐CMP kinase 2 inhibits ZIKV replication through activation of type I IFN signaling pathway

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