Hepatic expression of proteasome subunit alpha type‐6 is upregulated during viral hepatitis and putatively regulates the expression of <scp>ISG</scp>15 ubiquitin‐like modifier, a proviral host gene in hepatitis C virus infection

Broering, Ruth; Trippler, Martin; Werner, Melanie; Real, CI; Megger, Dominik A.; Bracht, Thilo; Schweinsberg, Vincent; Sitek, Barbara; Eisenacher, Martin; Meyer, Helmut E.; Baba, Hideo A.; Weber, Frank; Hoffmann, Andreas-Claudius; Gerken, Guido; Schlaak, J. F.

doi:10.1111/jvh.12508

Cited by 8 publications

(8 citation statements)

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“…In contrast, our study showed that ISG15 levels were positively correlated with viral loads, implying a contradictory effect of ISG15 on antiviral activities. This is consistent with studies showing that ISG15 can promote HCV replication [ 19 , 35 , 36 ].…”

Section: Discussionsupporting

confidence: 93%

“…ISG15 plays also a role in the response to many viral infections [9,15-18]. A recent study has shown that knockdown of ISG15 results in suppression of hepatitis C virus (HCV) replication in vitro by promoting the IFN response, suggesting involvement of ISG15 in regulating HCV replication [19,20]. Furthermore, patients who respond favorably to IFN treatment of hepatitis C have low expression levels of ISG15 and its conjugates in the liver compared to non-responders [21,22].…”

Section: Introductionmentioning

confidence: 99%

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Interferon-stimulated gene 15 in hepatitis B-related liver diseases

et al. 2016

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This study investigates the association of Interferon-stimulated gene 15 (ISG15) polymorphisms, ISG15 serum levels and expression with HBV-related liver diseases. The ISG15 promoter and the two exons of the gene were screened for polymorphisms in 766 HBV-infected patients and in 223 controls. Soluble ISG15 levels were measured by ELISA. ISG15 mRNA expression was quantified by qRT-PCR in 36 tumor and adjacent non-tumor tissues. The exon 2 allele rs1921A was found associated with decreased progression of HBV-related liver diseases (LC vs. CHB: OR = 0.6, 95%CI = 0.4-0.8, adjusted P = 0.003; HCC vs. CHB: OR = 0.6, 95%CI = 0.4-0.9, adjusted P = 0.005). The rs1921AA genotype was associated with low levels of AST, ALT and total bilirubin, but with high prothrombin levels (P < 0.05). ISG15 serum levels were higher among HBV patients compared to controls (P < 0.0001) and positively associated with HBV-related liver diseases, with highest levels among LC patients. ISG15 levels were correlated with HBV-DNA loads (P = 0.001). In non-tumor tissues from HCC patients, ISG15 mRNA expression was increased in HBV compared to non-HBV infection (P = 0.016). The ISG15 rs1921 variant and ISG15 expression are associated with HBV-related liver diseases. Taken together, ISG15 appears to be a proviral factor involved in HBV replication and triggering progression of HBV-related liver diseases.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Interferon-stimulated gene 15 in hepatitis B-related liver diseases

et al. 2016

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“…14 In addition, high levels of ISG15 in the liver of patients with HCV infection were associated with an unfavourable HCV genotype 1, a high hepatic HCV load and a low antiviral response to IFN compared to patients who did not present such characteristics. 13 These findings indicate the potential of ISG15 as a biomarker of IFN treatment response in patients with HCV infection.…”

Section: Illustrative Casementioning

confidence: 77%

“…12 Furthermore, upregulated expression of ISG15 was observed at both the mRNA and protein levels in liver tissue samples from patients with HCV infection compared to the levels detected in uninfected controls. 13 Similarly, the abundance of ISG15 transcripts was found to be increased in human PBMCs and liver cells in patients with HCV infection who were unresponsive to IFN treatment compared to the levels in corresponding IFN-responsive patients. 14 In addition, high levels of ISG15 in the liver of patients with HCV infection were associated with an unfavourable HCV genotype 1, a high hepatic HCV load and a low antiviral response to IFN compared to patients who did not present such characteristics.…”

Section: Illustrative Casementioning

confidence: 91%

Organizing gene literature retrieval, profiling, and visualization training workshops for early career researchers

et al. 2021

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Developing the skills needed to effectively search and extract information from biomedical literature is essential for early-career researchers. It is, for instance, on this basis that the novelty of experimental results, and therefore publishing opportunities, can be evaluated. Given the unprecedented volume of publications in the field of biomedical research, new systematic approaches need to be devised and adopted for the retrieval and curation of literature relevant to a specific theme. Here we describe a hands-on training curriculum aimed at retrieval, profiling, and visualization of literature associated with a given topic. This curriculum was implemented in a workshop in January 2021. We provide supporting material and step-by-step implementation guidelines with the ISG15 gene literature serving as an illustrative use case. Through participation in such a workshop, trainees can learn: 1) to build and troubleshoot PubMed queries in order to retrieve the literature associated with a gene of interest; 2) to identify key concepts relevant to given themes (such as cell types, diseases, and biological processes); 3) to measure the prevalence of these concepts in the gene literature; 4) to extract key information from relevant articles, and 5) to develop a background section or summary on the basis of this information. Finally, trainees can learn to consolidate the structured information captured through this process for presentation via an interactive web application.

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“…Boltjes et al (29) demonstrated that a direct interaction between HBsAg and KC resulted in HBsAg uptake, induction of cytokine production, and the induction of IFN-γ production by NK cells. Alternatively, phagocytosis of HBV itself or -infected hepatocytes by KC may allow intracellular TLR3 exposure to viral RNA (30, 31). …”

Section: Discussionmentioning

confidence: 99%

Elevated Expression of Chemokine CXCL13 in Chronic Hepatitis B Patients Links to Immune Control during Antiviral Therapy

et al. 2017

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C–X–C-chemokine ligand 13 (CXCL13), the ligand for C–X–C chemokine receptor type 5 (CXCR5), is a major regulator of B-cell trafficking and plays an integral role in age-dependent clearance of hepatitis B virus (HBV) in the mouse model. However, the expression and function of CXCL13 in patients with chronic hepatitis B (CHB) remain unknown. By use of liver cell subpopulations isolated from CHB patients, we found that CXCL13 mRNA was abundantly expressed in Kupffer cells (KCs), but not in primary hepatocytes, liver sinusoidal endothelial cells, and hepatic stellate cells. Interestingly, KC isolated from HBV-positive liver had much higher level of CXCL13 expression than non-HBV-infected controls. And its expression was induced by toll-like receptor 3 ligand poly I:C stimulation. Moreover, intense expression of CXCL13 protein and accumulation of CD4+ T and B cells were evident in follicular-like structures in the liver tissue of CHB patients, which indicated its chemotactic effect on CXCR5+ CD4+ cells and B cells. Consistently, the levels of serum CXCL13 were significantly higher in the CHB patients than in healthy controls. Furthermore, CXCL13 concentration was increased in the complete response (CR) group during weeks 0–12 and did not change significantly during the course of telbivudine treatment, compared with the patients who didn’t achieve CR. In conclusion, the HBV-related increase of CXCL13 production in KC and serum CXCL13 level during telbivudine treatment might be associated with immune control of chronic HBV infection.

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Hepatic expression of proteasome subunit alpha type‐6 is upregulated during viral hepatitis and putatively regulates the expression of ISG15 ubiquitin‐like modifier, a proviral host gene in hepatitis C virus infection

Cited by 8 publications

References 50 publications

Interferon-stimulated gene 15 in hepatitis B-related liver diseases

Interferon-stimulated gene 15 in hepatitis B-related liver diseases

Organizing gene literature retrieval, profiling, and visualization training workshops for early career researchers

Elevated Expression of Chemokine CXCL13 in Chronic Hepatitis B Patients Links to Immune Control during Antiviral Therapy

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