Overview
HCVPACK - DEVELOPMENT OF TWO COMPLEMENTARY SYSTEMS FOR THE STUDY OF RECOMBINATION AND PACKAGING OF HEPATITIS C VIRUS GENOMIC RNA USING FLUORESCENT PROTEINS AND LIVE IMAGING 

Time period:
2011-04-01 - 2015-03-31
Instrument:
Support for training and career development of researchers (Marie Curie)
Call:
Marie Curie Reintegration Grants

The Hepathitis C Virus (HCV) infects more than 150 million people worldwide and is the major cause of hepatic cirrhosis and hepatocellular carcinoma. Current available treatment options have limited efficacy and result in effective viral suppression only in about 50% of treated patients. In addition, HCV exhibits an extremely high genetic variability, mainly due to lack of proofreading activity of the viral RNA polymerase and its ability to generate recombinant genomes. Genetic diversity allows the virus to evolve variants capable to escape immune response and drug pressure and hampers the development of effective vaccines. Research of novel specific drugs is hindered by our limited understanding of several key steps of the viral life cycle. To clarify different aspects of HCV RNA biology, we propose the development of two new assays based on detection of fluorescent proteins. Our first objective is to use the reconstitution of a GFP protein to measure native recombination capability of HCV under different infection conditions. This part will clarify the relative importance of several factors in the generation on new recombinant forms. Subsequently, we will deploy a system to visualize genomic RNA and viral Core protein simultaneously in live cells. By fusing different fluorophores to RNA-binding proteins and to the Core, we will be able to measure packaging and copackaging efficiencies of HCV. Lastly, we will trace the pathway of RNA molecules and Core using live imaging. This will help identifying the sites of recombination, dimerization and packaging in the cell. Taken together, the data produced will help clarify several important aspects of the viral replication cycle, and identify possible new targets for antiviral intervention. Moreover, the systems proposed represent novel approaches to the study of RNA biology in HCV, providing the Copenhagen Hepatitis C Program with advanced and competitive know-how in the field of HCV research.

Principal investigators
Scientific co-ordinator:
Jens Bukh (REGION HOVEDSTADEN)

Related Areas

Countries
Denmark
Last updated on 2014-06-17 at 16:13