Researchers Identify Protein Key to Hepatitis C Virus Replication

by VR Sreeraman on Aug 17 2009 5:56 PM

Experts at Heidelberg University Hospital in Germany say that they have identified a protein in infected liver cells that is essential for the replication of the hepatitis C virus (HCV).

Writing about their work in the journal Public Library of Science Pathogens, they said that inhibiting the protein was highly efficient in blocking virus replication.

According to background information in the article, over 170 million people worldwide are affected by chronic hepatitis C, and, in up to 80 percent of infections, the virus can not be eliminated but persists in the infected individual.

The report further states that chronically infected persons have a high risk of developing serious liver inflammation, liver cirrhosis, and even a liver cell tumour.

An essential cell factor required for hepatitis C virus replication is cyclophilin, which promotes the proper folding of proteins and the formation of large protein assemblies, adds the report.

The researchers say that they analysed liver cells to determine which variant of cyclophilins is critical for hepatitis C virus replication, and found that blocking cyclophilin A leads complete inhibition of virus replication.

They have also found this cyclophilin to be the target of DEBIO-025, a derivative of the immunosuppressant cyclosporin, which is used primarily in the context of organ transplantation.

The researchers say that two complementary effects are responsible for the inhibition of hepatitis C virus replication: cyclophilin A is required both for the formation of the viral replication machinery and for the activity of a viral enzyme that is essential for the assembly of infectious virus particles.

According to them, inhibiting cyclophilin A with DEBIO-025 thus blocks hepatitis C virus replication from two different sides.

By contrast, blocking cyclophilin B had no effect.

"The therapeutic potential of inhibiting cellular factors essential for virus replication has thus far hardly been tapped. But this approach has the major advantage that resistance arises less frequently and to a lesser extent in comparison to therapies directly targeting viral factors," says Professor Bartenschlager.