HCV modifies EGF signalling and upregulates production of CXCR2 ligands: Role in inflammation and antiviral immune response

Groepper, Christina; Rufinatscha, Kerstin; Schröder, Nadja; Stindt, S; Ehlting, Christian; Albrecht, Ute; Bock, Hans H.; Bartenschlager, Ralf; Häussinger, Dieter; Bode, Johannes G.

doi:10.1016/j.jhep.2018.04.005

Cited by 11 publications

(11 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We suggested the involvement of the EGFR signaling pathway as a mechanism that may induce epigenetic changes in HCV infected cells, for a number of reasons. First, previous reports demonstrated the activation of EGFR by HCV proteins [70][71][72][73][74][75]. We have recently demonstrated that HCV infection constitutively activates EGFR thus inducing invasion of HCV-infected cells [76].…”

Section: Possible Mechanisms Of Epigenetic Imprinting By Hcv Infection: Paving the Way For Hcc Prevention?mentioning

confidence: 93%

Tracking Down the Epigenetic Footprint of HCV-Induced Hepatocarcinogenesis

Domovitz

Gal-Tanamy

2021

JCM

View full text Add to dashboard Cite

Hepatitis C virus (HCV) is a major cause of death and morbidity globally and is a leading cause of hepatocellular carcinoma (HCC). Incidence of HCV infections, as well as HCV-related liver diseases, are increasing. Although now, with new direct acting antivirals (DAAs) therapy available, HCV is a curable cancer-associated infectious agent, HCC prevalence is expected to continue to rise because HCC risk still persists after HCV cure. Understanding the factors that lead from HCV infection to HCC pre- and post-cure may open-up opportunities to novel strategies for HCC prevention. Herein, we provide an overview of the reported evidence for the induction of alterations in the transcriptome of host cells via epigenetic dysregulation by HCV infection and describe recent reports linking the residual risk for HCC post-cure with a persistent HCV-induced epigenetic signature. Specifically, we discuss the contribution of the epigenetic changes identified following HCV infection to HCC risk pre- and post-cure, the molecular pathways that are epigenetically altered, the downstream effects on expression of cancer-related genes, the identification of targets to prevent or revert this cancer-inducing epigenetic signature, and the potential contribution of these studies to early prognosis and prevention of HCC as an approach for reducing HCC-related mortality.

show abstract

Section: Possible Mechanisms Of Epigenetic Imprinting By Hcv Infection: Paving the Way For Hcc Prevention?mentioning

confidence: 93%

Tracking Down the Epigenetic Footprint of HCV-Induced Hepatocarcinogenesis

Domovitz

Gal-Tanamy

2021

JCM

View full text Add to dashboard Cite

show abstract

“…EGFR activity is prolonged by the NS5A-mediated alteration of EGFR trafficking [56] and by stimulated Netrin-1 expression, which impedes EGFR recycling [57]. Moreover, HCV replication itself promotes the expression of the receptor ligand EGF [58]. Additionally, NS3/4A activity induces the proteolytic cleavage of the EGFR phosphatase T cell protein tyrosine phosphatase (TC-PTP), thus sustaining EGFR activation [59].…”

Section: Egf Signaling Pathwaymentioning

confidence: 99%

Hepatitis C Virus and Hepatocellular Carcinoma: When the Host Loses Its Grip

Goto

Suarez

Wrensch

et al. 2020

IJMS

View full text Add to dashboard Cite

Chronic infection with hepatitis C virus (HCV) is a major cause of hepatocellular carcinoma (HCC). Novel treatments with direct-acting antivirals achieve high rates of sustained virologic response; however, the HCC risk remains elevated in cured patients, especially those with advanced liver disease. Long-term HCV infection causes a persistent and accumulating damage of the liver due to a combination of direct and indirect pro-oncogenic mechanisms. This review describes the processes involved in virus-induced disease progression by viral proteins, derailed signaling, immunity, and persistent epigenetic deregulation, which may be instrumental to develop urgently needed prognostic biomarkers and as targets for novel chemopreventive therapies.

show abstract

“…Other, more mechanistic studies published by the Bode group [16,26,39] showed that NS3/4A promotes secretion of chemokines and proinflammatory cytokines via cleavage of PTPN2, which acts as a negative regulator of these molecules. These studies also indicate that PTPN2 cleavage by NS3/4 results in a shift from an antiviral Th1 toward a Th2 immune response, finally promoting viral replication and persistence [26].…”

Section: Discussionmentioning

confidence: 98%

Protein Tyrosine Phosphatase Nonreceptor Type 2 Expression Does Not Correlate with Viral Load or Response to Direct-Acting Antiviral Therapy in Hepatitis C Virus Infections-Infected Patients

et al. 2020

View full text Add to dashboard Cite

Background/Aims: The hepatitis C virus nonstructural 3/4A protease has been shown to cleave protein tyrosine phosphatase nonreceptor type 2 (PTPN2, also known as T cell protein tyrosine phosphatase), thereby inducing a shift from a Th1 toward a nonantiviral Th2 immunity. Ribavirin therapy reverses these effects and supports direct-acting antiviral (DAA) therapy as an immunomodulatory compound and ultimately improves the response to DAA therapy. Here we aimed to assess whether intrahepatic levels of PTPN2 might be used as a clinical prognostic marker for the response to DAA therapy. Methods: Liver biopsies from hepatitis C virus-infected patients with and without cirrhosis were immunohistochemically stained for PTPN2 and scored for staining intensity as well as percentage of hepatocytes positive for nuclear PTPN2 localization. PTPN2 scores were correlated to sustained virologic response after DAA therapy, viral load, serum levels of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase (GGT), and the Model for End-Stage Liver Disease (MELD) score at the time of liver biopsy. Results: We did not detect a difference in intrahepatic PTPN2 levels between responders with cirrhosis, responders without cirrhosis, and nonresponders to DAA therapy. There was no correlation between intrahepatic PTPN2 levels and viral load or clinical markers such as liver transaminases, GGT, or the MELD score. Conclusion: Intrahepatic PTPN2 levels assessed via IHC staining do not represent a clinical prognostic marker for the response to DAA therapy.

show abstract

HCV modifies EGF signalling and upregulates production of CXCR2 ligands: Role in inflammation and antiviral immune response

Cited by 11 publications

References 36 publications

Tracking Down the Epigenetic Footprint of HCV-Induced Hepatocarcinogenesis

Tracking Down the Epigenetic Footprint of HCV-Induced Hepatocarcinogenesis

Hepatitis C Virus and Hepatocellular Carcinoma: When the Host Loses Its Grip

Protein Tyrosine Phosphatase Nonreceptor Type 2 Expression Does Not Correlate with Viral Load or Response to Direct-Acting Antiviral Therapy in Hepatitis C Virus Infections-Infected Patients

Contact Info

Product

Resources

About