scholarly journals Alpha Interferon Inhibits Hepatitis C Virus Replication in Primary Human Hepatocytes Infected In Vitro

2002 ◽  
Vol 76 (16) ◽  
pp. 8189-8199 ◽  
Author(s):  
Valérie Castet ◽  
Chantal Fournier ◽  
Alexandre Soulier ◽  
Rozenn Brillet ◽  
Joliette Coste ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Primary Cultures ◽  
Indirect Evidence ◽  
Human Hepatocytes ◽  
Alpha Interferon ◽  
Healthy Human

ABSTRACT Chronic hepatitis C is a common cause of liver disease, the complications of which include cirrhosis and hepatocellular carcinoma. Treatment of chronic hepatitis C is based on the use of alpha interferon (IFN-α). Recently, indirect evidence based on mathematical modeling of hepatitis C virus (HCV) dynamics during human IFN-α therapy suggested that the major initial effect of IFN-α is to block HCV virion production or release. Here, we used primary cultures of healthy, uninfected human hepatocytes to show that: (i) healthy human hepatocytes can be infected in vitro and support HCV genome replication, (ii) hepatocyte treatment with IFN-α results in expression of IFN-α-induced genes, and (iii) IFN-α inhibits HCV replication in infected human hepatocytes. These results show that IFN-α acts primarily through its nonspecific antiviral effects and suggest that primary cultures of human hepatocytes may provide a good model to study intrinsic HCV resistance to IFN-α.

Circulating and inducible IL-32α in chronic hepatitis C virus infection

2019 ◽  
Vol 2 (1) ◽  
pp. 23-30
Author(s):  
Mark Collister ◽  
Julia Rempel ◽  
Jiaqi Yang ◽  
Kelly Kaita ◽  
Zach Raizman ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Chronic Hepatitis C Virus ◽  
Chronic Hcv

Background: Interleukin 32 (IL-32) is a recently described pro-inflammatory cytokine implicated in chronic hepatitis C virus (HCV)-related inflammation and fibrosis. IL-32α is the most abundant IL-32 isoform. Methods: Circulating IL-32α levels were documented in patients with chronic HCV infections ( n = 31) and compared with individuals who spontaneously resolved HCV infection ( n = 14) and HCV-naive controls ( n = 20). In addition, peripheral blood mononuclear cells (PBMC) from the chronic HCV ( n = 12) and HCV-naive ( n = 9) cohorts were investigated for responses to HCV core and non-structural (NS)3 protein induced IL-32α production. Finally, correlations between IL-32α levels, hepatic fibrosis and subsequent responses to interferon-based therapy were documented in patients with chronic HCV. Results: Circulating IL-32α levels in patients with chronic HCV were similar to those of spontaneously resolved and HCV-naive controls. HCV protein induced IL-32α responses were similar in chronic HCV patients and HCV-naive controls. In patients with chronic HCV, serum IL-32α levels correlated with worsening METAVIR fibrosis (F) scores from F0 to F3 ( r = 0.596, P < 0.001) as did NS3 induced IL-32α responses ( r = 0.837, P < 0.05). However, these correlations were not sustained with the inclusion of IL-32α levels at F4 scores, suggesting events at F4 interfere with IL-32α synthesis or release. In chronic HCV patients who underwent treatment ( n = 28), baseline in vivo and in vitro induced IL-32α concentrations were not predictive of therapeutic outcomes. Conclusions: IL-32α activity is associated with worsening fibrosis scores in non-cirrhotic, chronic HCV patients.

In vitro secretion of anti-GOR protein and anti-hepatitis C virus antibodies in patients with chronic hepatitis C

1994 ◽  
Vol 107 (5) ◽  
pp. 1443-1448 ◽  
Author(s):  
Hanns F. Löhr ◽  
Guido Gerken ◽  
Gerd Michel ◽  
Hans-Bertram Braun ◽  
Karl-Hermann Meyer Zum Büschenfelde
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Chronic Hepatitis C

HLA class II genotypes associated with chronic hepatitis C virus infection and response to alpha-interferon treatment in Poland

2000 ◽  
Vol 20 (3) ◽  
pp. 234-239 ◽  
Author(s):  
Marta Wawrzynowicz-Syczewska ◽  
James A. Underhill ◽  
Michael A. Clare ◽  
Anna Boron-Kaczmarska ◽  
Ian G. McFarlane ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Infection ◽  
Chronic Hepatitis C ◽  
Hla Class Ii ◽  
Alpha Interferon ◽  
Interferon Treatment ◽  
Hepatitis C Virus Infection ◽  
Chronic Hepatitis C Virus

scholarly journals Synergy of Small Molecular Inhibitors of Hepatitis C Virus Replication Directed at Multiple Viral Targets

2006 ◽  
Vol 81 (6) ◽  
pp. 3005-3008 ◽  
Author(s):  
David L. Wyles ◽  
Kelly A. Kaihara ◽  
Florin Vaida ◽  
Robert T. Schooley
Keyword(s):  
Clinical Trials ◽  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Mechanisms Of Action ◽  
Systematic Assessment ◽  
Chronic Hepatitis C Virus ◽  
Small Molecular Inhibitors

ABSTRACT Chronic hepatitis C virus (HCV) infection is a significant worldwide health problem with limited therapeutic options. A number of novel, small molecular inhibitors of HCV replication are now entering early clinical trials in humans. Resistance to small molecular inhibitors is likely to be a significant hurdle to their use in patients. A systematic assessment of combinations of interferon and/or novel anti-hepatitis C virus agents from several different mechanistic classes was performed in vitro. Combinations of inhibitors with different mechanisms of action consistently demonstrated more synergy than did compounds with similar mechanisms of action. These results suggest that combinations of inhibitors with different mechanisms of action should be prioritized for assessment in clinical trials for chronic hepatitis C virus infection.

Early prediction of successful alpha-interferon therapy of chronic hepatitis C by core-IgM antibodies to hepatitis C virus

1994 ◽  
Vol 20 (2) ◽  
pp. 305-306 ◽  
Author(s):  
Nicolaos C. Tassopoulos ◽  
Angelos E. Hatzakis ◽  
George V. Papatheodoridis ◽  
Gerassimos Karvountzis ◽  
Hugo Troonen ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Interferon Therapy ◽  
Alpha Interferon ◽  
Early Prediction ◽  
Igm Antibodies

scholarly journals Differential Expression of the CXCR3 Ligands in Chronic Hepatitis C Virus (HCV) Infection and Their Modulation by HCV In Vitro

2008 ◽  
Vol 83 (2) ◽  
pp. 836-846 ◽  
Author(s):  
Karla J. Helbig ◽  
Andrew Ruszkiewicz ◽  
Robert E. Lanford ◽  
Mark D. Berzsenyi ◽  
Hugh A. Harley ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Hcv Infection ◽  
Chemokine Expression ◽  
Tnf Α ◽  
Chronic Hepatitis C Virus ◽  
Ifn Γ

ABSTRACT To investigate chemokine expression networks in chronic hepatitis C virus (HCV) infection, we used microarray analysis to determine chemokine expression in human infection and in chimpanzees experimentally infected with HCV. The CXCR3 chemokine family was highly expressed in both human and chimpanzee infection. CXCL10 was the only CXCR3 chemokine elevated in the serum, suggesting that it may neutralize any CXCR3 chemokine gradient established between the periphery and liver by CXCL11 and CXCL9. Thus, CXCR3 chemokines may not be responsible for recruitment of T lymphocytes but may play a role in positioning these cells within the liver. The importance of the CXCR3 chemokines, in particular CXCL11, was highlighted by replicating HCV (JFH-1) to selectively upregulate its expression in response to gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α). This selective upregulation was confirmed at the transcriptional level by using the CXCL11 promoter driving the luciferase reporter gene. This synergistic increase in expression was not a result of HCV protein expression but the nonspecific innate response to double-stranded RNA (dsRNA), as both in vitro-transcribed HCV RNA and the dsRNA analogue poly(I:C) increased CXCL11 expression and promoter activity. Furthermore, we show that CXCL11 is an IRF3 (interferon regulatory factor 3) response gene whose expression is selectively enhanced by IFN-γ and TNF-α. In conclusion, the CXCR3 chemokines are the most significantly expressed chemokines in chronic hepatitis C and most likely play a role in positioning T cells in the liver. Furthermore, HCV can selectively increase CXCL11 expression in response to IFN-γ and TNF-α stimulation that may play a role in the pathogenesis of HCV-related liver disease.

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