1155 PRIMARY HUMAN HEPATOCYTES AND CLINICAL STRAINS OF HEPATITIS C VIRUS: A HIGHLY RELEVANT IN VITRO MODEL FOR ANTIVIRAL DRUG DEVELOPMENT

2013 ◽  
Vol 58 ◽  
pp. S469-S470
Author(s):  
C. Gondeau ◽  
P. Briolotti ◽  
P.-A. Rubbo ◽  
M.-P. Ripault ◽  
J.-M. Fabre ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Drug Development ◽  
In Vitro Model ◽  
Antiviral Drug ◽  
Human Hepatocytes ◽  
Clinical Strains ◽  
Primary Human Hepatocytes ◽  
Vitro Model

scholarly journals Future Directions in the Treatment of Patients with Chronic Hepatitis C Virus Infection

1999 ◽  
Vol 13 (1) ◽  
pp. 57-62 ◽  
Author(s):  
Robert G Gish
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
High Throughput Screening ◽  
In Vitro Model ◽  
Single Agent ◽  
Protein Translation ◽  
In Vitro Translation ◽  
Biotechnology Companies ◽  
Vitro Model

Hepatitis C virus (HCV) infects over 170 million people worldwide. While interferon is currently the most used single agent therapy, this drug may result in a sustained loss of virus from the blood in only up to 15% of patients; new options for treatment are needed. With the release of ribavirin in North America and Europe, a viral clearance rate or ‘cure’ may be attained in up to 40% of patients. Developing successful antiviral therapy that prevents or delays the development of cirrhosis, liver failure and liver cancer as well as decreasing the demand for liver transplantation are clearly identified goals. Unfortunately, there is no complete in vitro model of HCV replication or translation. Due to the lack of an animal or cell culture model of HCV infection, in vitro translation screening systems to identify inhibitors of HCV protein translation are being evaluated by a large number of biotechnology companies. With advancing computer technology, high throughput screening processes are now possible and can be joined to specific in vitro model testing systems. Along with examining some of the information known about HCV therapy and the HCV genome, the present review discusses potential targets for new therapies and identifies therapeutic agents that are nearing clinical application

scholarly journals An in vitro model of hepatitis C virus genotype 3a-associated triglycerides accumulation

2005 ◽  
Vol 42 (5) ◽  
pp. 744-751 ◽  
Author(s):  
Karim Abid ◽  
Valerio Pazienza ◽  
Andrea de Gottardi ◽  
Laura Rubbia-Brandt ◽  
Beatrice Conne ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
In Vitro Model ◽  
Virus Genotype ◽  
Vitro Model ◽  
Genotype 3A

868 LIVER X RECEPTOR a-MEDIATED LIPOGENESIS INDUCED BY HEPATITIS C VIRUS NS5A AND CORE PROTEINS REGULATES VIRAL REPLICATION IN AN IN VITRO MODEL

2012 ◽  
Vol 56 ◽  
pp. S338
Author(s):  
S. Pisonero-Vaquero ◽  
M.V. García-Mediavilla ◽  
F. Jorquera ◽  
P.L. Majano ◽  
J. Gonzalez-Gallego ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Viral Replication ◽  
In Vitro Model ◽  
Liver X Receptor ◽  
Core Proteins ◽  
Vitro Model

scholarly journals In-vitro model systems to study Hepatitis C Virus

2011 ◽  
Vol 9 (1) ◽  
Author(s):  
Usman Ali Ashfaq ◽  
Shaheen N Khan ◽  
Zafar Nawaz ◽  
Sheikh Riazuddin
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
In Vitro Model ◽  
Model Systems ◽  
Vitro Model

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.

Long-term functional maintenance of primary human hepatocytes in vitro

Science ◽  
2019 ◽  
Vol 364 (6438) ◽  
pp. 399-402 ◽  
Author(s):  
Chengang Xiang ◽  
Yuanyuan Du ◽  
Gaofan Meng ◽  
Liew Soon Yi ◽  
Shicheng Sun ◽  
...  
Keyword(s):  
Cell Biology ◽  
Expression Profiles ◽  
Antiviral Drug ◽  
Gene Expression Profiles ◽  
Global Gene Expression ◽  
Human Hepatocytes ◽  
Hbv Infection ◽  
Primary Human Hepatocytes

The maintenance of terminally differentiated cells, especially hepatocytes, in vitro has proven challenging. Here we demonstrated the long-term in vitro maintenance of primary human hepatocytes (PHHs) by modulating cell signaling pathways with a combination of five chemicals (5C). 5C-cultured PHHs showed global gene expression profiles and hepatocyte-specific functions resembling those of freshly isolated counterparts. Furthermore, these cells efficiently recapitulated the entire course of hepatitis B virus (HBV) infection over 4 weeks with the production of infectious viral particles and formation of HBV covalently closed circular DNA. Our study demonstrates that, with a chemical approach, functional maintenance of PHHs supports long-term HBV infection in vitro, providing an efficient platform for investigating HBV cell biology and antiviral drug screening.

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