Chimeric GB virus B (GBV-B) : use in the development of treatments targeting Hepatitis C virus infection
Inventor: Annette MARTIN et al
Hepatitis C virus (HCV), a flavivirus, causes chronic hepatitis C and is a major public health threat . In the US, nearly 4 million people are chronically infected with HCV, with 8-10,000 deaths annually. Although worldwide prevalence varies considerably by geographic region, it is estimated that more than 3% of the global population is infected. Many HCV infections are asymptomatic, however, infected individuals are at increased risk of developing cirrhosis and/or liver cancer.
Available HCV therapies include IFN-a and ribavirin, but their efficacy is limited, and even lengthy treatment frequently fails to achieve virus elimination. Unfortunately, the search for better and more specific antiviral therapies is complicated by the lack of an efficient cell culture system for the virus and by the expense and limited availability of chimpanzees, the sole animal model for HCV. Because of these limitations, researchers working on HCV treatment and prevention are using surrogate virus models in HCV drug discovery efforts.
Description of invention:
GB virus B (GBV-B) is a hepatotropic flavivirus and a close relative of HCV. GBV-B causes acute hepatitis in experimentally infected tamarins and can serve as a surrogate virus for HCV in drug screening. In the present invention, researchers at the Institut Pasteur and collaborators at the University of Texas have constructed a full length viable clone of GBV-B, which includes a 3’ terminal sequence of GBV-B that was missing from earlier cloning attempts. The investigators have developed various chimeric constructs containing selected regions of the HCV genome within the background of GBV-B. Some of these chimera were found to be infectious and pathogenic for tamarins. It is believed these chimeric GBV-B HCV constructs will be very useful for the development of HCV preventative and therapeutic treatments targeting specific HCV domains (encoding envelope, protease, and polymerase proteins).
Potential application and advantages:
GBV-B can be used as a model for HCV, and the GBV-B genome can be used as the acceptor molecule in the construction of chimeric viral RNAs. These chimera will allow investigation of potential inhibitors of specific HCV activities linked to inserted HCVdomains.
Tamarin is a less costly, more practical animal model than chimpanzee to test new drugs.
Recent pertinent publications:
Martin A et al. Proc Natl Acad Sci U S A. 2003 Aug 19;100(17):9962-7. Epub 2003 Aug 07.
US patent application filed July 3, 2002, published Feb. 26, 2004 as US20040039187A1
US patent application filed on September 27, 2004
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