HCV/HIV-PI
The impact of HCV diversity on replication fitness and protease inhibitor sensitivity in HIV infected patients with chronic HCV
| Coordinatore |
Organization address
address: Sinesio Delgado 10 contact info |
| Nazionalità Coordinatore | Non specificata |
| Totale costo | 208˙351 € |
| EC contributo | 208 € |
| Programma | FP7-PEOPLE
Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) |
| Anno di inizio | 2008 |
| Periodo (anno-mese-giorno) | 2008-08-01 - 2010-07-31 |
Partecipanti
| # | ||||
|---|---|---|---|---|
| 1 |
FUNDACION PARA LA INVESTIGACION BIOMEDICA DEL HOSPITAL CARLOS III
Organization address
address: Sinesio Delgado 10 contact info |
ES (MADRID) | coordinator | 0.00 |
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Obiettivo del progetto (Objective)
'Hepatitis C virus (HCV) is a major cause of premature death due to cirrhosis and hepatocellular carcinoma in a large proportion of the world population (>25 million). Recently, advances in the development of new therapeutic compounds to treat HCV have revealed several potent inhibitors of the HCV serine protease, which have reached clinical trials. However HCV has a high genetic variability, not only between genotypes but also between quasispecies of an infected individual. In HIV coinfected patients the levels of complexity and diversity of the HCV protease gene variants and the resultant impact on HIV coinfection are unknown. The advent of HCV genotype 1b derived replicon systems has enabled measurement of HCV subgenomic RNA replication in a cell-based format and aided the development in the new therapeutic compounds. However these replicons are not representative of the genetic variability within the HCV genotypes, subtypes and quasispecies. In this project proposal we wish to clone HCV NS3 sequences derived from the sera of HIV infected patients with chronic HCV to address the impact of diversity on replication fitness and the drug sensitivity in a transient replication assay. The importance of HIV co-infection will also be investigated. The project will take place in the Center for the Study of Hepatitis C, New York, USA were the state of the art techniques are currently being used. In the returning phase the methodology and experience will be transferred to Europe at the Hospital Carlos III, Madrid, Spain an institute renown for its research in HIV and viral hepatitis co-infection. This project will help understanding the mechanism of HCV drug resistance and will provide relevant information for the design of new anti-HCV drugs'
Introduzione (Teaser)
The existence of different strains of a virus can render drug therapy ineffective, as is very much the case with the hepatitis C virus. Moreover, treatment is potentially complicated as many chronic sufferers are also infected with HIV.
Descrizione progetto (Article)
The hepatitis C virus (HCV) causes death through liver cirrhosis and cancer in more than 25 million people worldwide. There are many strains of HCV, and difficulties in finding effective therapies are further compounded because all patients are genetically different.
New medicines to treat HCV include those that actively inhibit the production of HCV serine protease, a protein essential for completion of the life cycle of the virus in the infected person. However, the genetic complexity of the situation may interfere with the drug's effectiveness. Moreover, co-infection with HIV may also hamper the drug's action.
Another protein with a crucial role in virus replication is NS3. This puts it in the league of a viable drug target. However, some NS3 proteins produced by the virus are potentially resistant to inhibitors.
Scientists can now replicate the virus in isolated cells. Using this system, the HCV/HIV-PI project team cloned HCV NS3 sequences from infected patients to investigate how genetic diversity impacts the ability of the virus to multiply. The researchers also gauged the sensitivity to drugs in the different genotypes.
No significant differences were found in NS3 in patients with both HIV and hepatitis C infections as opposed to those with HCV only. Replication of the virus in the lab was highly successful. Even when mutations were incorporated into HCV, replication of the virus was at a similar level as a wild type strain.
The results of the HCV/HIV-PI research will prove invaluable to the search for new drugs to tackle the mounting problem of viral infection in world health. Testing in the lab will help to circumvent the time-consuming laborious process of drug testing on animal models and human patients.