scholarly journals Impaired antiviral activity of interferon alpha against hepatitis C virus 2a in Huh-7 cells with a defective Jak-Stat pathway

2010 ◽  
Vol 7 (1) ◽  
pp. 36 ◽  
Author(s):  
Sidhartha Hazari ◽  
Partha K Chandra ◽  
Bret Poat ◽  
Sibnarayan Datta ◽  
Robert F Garry ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Activity ◽  
Interferon Alpha ◽  
Stat Pathway

Involvement of ERK pathway in interferon alpha-mediated antiviral activity against hepatitis C virus

Cytokine ◽  
2015 ◽  
Vol 72 (1) ◽  
pp. 17-24 ◽  
Author(s):  
Lan-Juan Zhao ◽  
Wen Wang ◽  
Wen-Bo Wang ◽  
Hao Ren ◽  
Zhong-Tian Qi
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Activity ◽  
Interferon Alpha ◽  
Erk Pathway

scholarly journals Inhibition of STAT Pathway Impairs Anti-Hepatitis C Virus Effect of Interferon Alpha

2016 ◽  
Vol 40 (1-2) ◽  
pp. 77-90 ◽  
Author(s):  
Lan-Juan Zhao ◽  
Sheng-Fei He ◽  
Yuan Liu ◽  
Ping Zhao ◽  
Zhong-Qi Bian ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Interferon Alpha ◽  
Hcv Infection ◽  
Hcv Rna ◽  
Jak Inhibitor ◽  
Stat Signaling ◽  
Antiviral Gene ◽  
Stat Pathway

Background/Aims: Signal transducer and activator of transcription (STAT) pathway plays an important role in antiviral efficacy of interferon alpha (IFN-α). IFN-α is the main therapeutic against hepatitis C virus (HCV) infection. We explored effects of IFN-α on HCV replication and antiviral gene expression by targeting STAT. Methods: In response to IFN-α, STAT status, HCV replication, and antiviral gene expression were analyzed in human hepatoma Huh7.5.1 cells before and after cell culture-derived HCV infection. Results: IFN-α treatment induced expression and phosphorylation of STAT1 and STAT2 in Huh7.5.1 cells. Pretreatment of Huh7.5.1 cells with a mAb to IFN alpha receptor (IFNAR) 2 decreased IFN-α-dependent phosphorylation of STAT1 and STAT2, whereas pretreatment with an IFNAR1 mAb increased such phosphorylation, suggesting that IFNAR mediates IFN-α-triggered STAT signaling. During HCV infection, STAT1 and STAT2 phosphorylation could be rescued by IFN-α and IFN-α-induced phosphorylation of STAT1 and STAT2 was impaired. Inhibition of STAT pathway by Jak inhibitor I significantly enhanced HCV RNA replication and viral protein expression. Antiviral genes coding for IFN regulatory factor 9 and IFN-stimulated gene 15 were up-regulated by IFN-α during HCV infection but such up-regulation was abrogated by Jak inhibitor I. Conclusion: These results establish that activation of STAT pathway is essential for anti-HCV efficacy of IFN-α. Impairment of IFN-α-triggered STAT signaling by HCV may account for evading IFN-α response.

scholarly journals Free fatty acids induce ER stress and block antiviral activity of interferon alpha against hepatitis C virus in cell culture

2012 ◽  
Vol 9 (1) ◽  
pp. 143 ◽  
Author(s):  
Feyza Gunduz ◽  
Fatma M Aboulnasr ◽  
Partha K Chandra ◽  
Sidhartha Hazari ◽  
Bret Poat ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Cell Culture ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Activity ◽  
Er Stress ◽  
Free Fatty Acids ◽  
Interferon Alpha

Die chronische Hepatitis-C-Infektion: Häufigkeit, Verlauf und Stand der Behandlungsmöglichkeiten bei Patienten mit intravenöser Drogenabhängigkeit

2005 ◽  
Vol 51 (2) ◽  
pp. 97-108 ◽  
Author(s):  
Martin Schäfer ◽  
Thomas Berg
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Interferon Alpha ◽  
Prospektive Studien ◽  
Chronische Hepatitis ◽  
Chronische Hepatitis C

<B>Ziel:</B> Übersicht zur Problematik der chronischen Hepatitis-C-Virus-(HCV)-Infektion bei Patienten mit intravenöser Drogenabhängigkeit. </P><P><B>Methodik:</B> Zusammenfassung und Interpretation aktueller Studien zur Epidemiologie und Therapie. </P><P><B>Ergebnisse:</B> HCV-infizierte drogenabhängige Patienten werden häufig von einer Therapie mit (Peg)-Interferon-alpha und Ribavirin ausgeschlossen. Studien der letzten Jahre zeigen jedoch, dass insbesondere bei Patienten in Methadonsubstitution Heilungsraten erzielt werden können, die vergleichbar sind mit langfristigen Ansprechraten in Kollektiven ohne Suchterkrankung. </P><P><B>Schlussfolgerungen:</B> Chronisch HCV-infizierte Patienten mit einer Drogenabhängigkeit müssen bei individueller Therapieentscheidung und interdisziplinärer Betreuung nicht von einer antiviralen Therapie ausgeschlossen werden. Weitere prospektive Studien werden jedoch benötigt.

Funktion von CEACAM-1 im Rahmen der Therapie der Hepatitis C-Virus Infektion mit Interferon-alpha in vivo und in vitro

2006 ◽  
Vol 44 (08) ◽  
Author(s):  
P Hilgard ◽  
R Bröring ◽  
M Trippler ◽  
S Viazov ◽  
G Gerken ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Interferon Alpha

Hepatitis C Virus Infektion nach Lebertransplantation – Verlauf unter früher antiviraler Kombinationstherapie mit Interferon-alpha und Ribavirin

2006 ◽  
Vol 44 (08) ◽  
Author(s):  
T Zimmermann ◽  
AP Barreiros ◽  
G Greif-Higer ◽  
M Wörns ◽  
C Mönch ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Interferon Alpha

Effects of Smoking on Pegylated Interferon alpha 2a and First Generation Protease Inhibitor-based Antiviral Therapy in Naïve Patients Infected with Hepatitis C Virus Genotype 1

2016 ◽  
Vol 25 (1) ◽  
pp. 15-24 ◽  
Author(s):  
Tim Zimmermann ◽  
Dietrich Hueppe ◽  
Stefan Mauss ◽  
Peter Buggisch ◽  
Heike Pfeiffer-Vornkahl ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Therapy ◽  
Interferon Alpha ◽  
Virological Response ◽  
Sustained Viral Response ◽  
Pegylated Interferon ◽  
Genotype 1 ◽  
Pegylated Interferon Alpha ◽  
Viral Response

Background & Aims: Smoking has multiple effects on factors influencing hepatitis C and antiviral therapy, including lipid metabolism, fibrosis, platelet count and adherence aspects. The aim of this analysis was to determine the impact of smoking on hepatitis C virus antiviral therapy. Methods: Data of two cohorts of an observational multicenter study including therapy-naïve patients infected with genotype 1 hepatitis C virus (HCV) treated with dual antiviral therapy (n=7,796) with pegylated interferon alpha 2a in combination with ribavirin, or triple antiviral therapy (n=1,122) containing telaprevir or boceprevir, were analysed. Results: In the univariate matched pair analysis of dual antiviral therapy patients (n=584), smoking was significantly associated with lower sustained viral response rates (p=0.026, OR 0.69 CI: 0.50 – 0.96). The effect of smoking on sustained viral response remained significant (p=0.028, OR 0.67 CI: 0.47 – 0.96) in the multivariate analysis when adjusting for all other baseline parameters with a significant association in the univariate analysis, i.e. diabetes, fibrosis, body mass index, transaminases and baseline viral load. Under protease inhibitors the influence of smoking on virological response did not arise. Conclusions: Smoking has a negative impact on antiviral therapy in naïve patients infected with HCV genotype 1 independently of age, gender, history of drug use or alcoholic liver disease. The effects of smoking might be overcome by the new antiviral agents.Abbreviations: APRI: AST to platelet ratio index; DAA: direct antiviral agent; DT: dual antiviral therapy; EoTR: end of treatment response; RVR: rapid virological response; EVR: early virological response; HCV: hepatitis C virus; IFN: interferon alpha; MPA: Matched Pair Analysis; NS: non-smokers; PEG-IFN: pegylated interferon alpha 2a; PI: protease inhibitor; RBV: ribavirin; SAE: serious adverse event; SOC: standard of care; S: smokers; SVR: sustained viral response.    

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