Breaking the Hepatitis C lifecycle

Friday, 7 February, 2014
Cirrhosis, liver failure and liver cancer are just some of the many life-threatening conditions caused by the Hepatitis C Virus (HCV).

Unlike Hepatitis A and B there is no vaccine, and although new treatments for HCV are more effective, they still have harmful side effects. There are however high hopes that new research into how the virus reproduces in the body could lead to better treatments.

Treatments for HCV involve a cocktail of drugs – usually a combination of interferon and ribavirin and an antiviral (protease inhibitor). But this combination is not always effective in killing the virus, has debilitating side effects and is expensive, says Dr Ella Sklan, a researcher in the Department of Clinical Microbiology and Immunology at Tel Aviv University in Israel. Newer therapies, including interferon-free regimens, are in the pipeline, but have not yet been approved.        

Dr Sklan and her colleagues recently concluded an EU-funded research project, HCV Host Trafficking, on the potential of a different approach to treating HCV infection.

Her goal was to identify host cell proteins that the HCV virus needs to reproduce within the human body. A better understanding of the way the virus replicates could lay the groundwork for more effective treatments for the disease – with fewer side effects.

“I am interested in knowing how the virus interacts with the host cell and how it uses its system to reproduce", Sklan says. “In this study we found aspects of this interaction and how they affect the viral lifecycle. This will help in understanding the virus' vulnerable points and might identify new drug targets.

Sklan used several approaches to inhibit the proteins responsible for carrying the virus between host cells, thus significantly hindering viral replication.

One of the biggest problems with antiviral therapies is the evolution of drug-resistant strains. Drug cocktails are one way of approaching this problem, making it difficult for the virus to become resistant to all three drugs in the mix.

Another approach is to aim the drugs at the host, or the virus host interface (the points of interaction between the virus and its host cell), which is not under the control of the virus. Treatments like these should have a much higher resistance barrier. Based on work conducted in HCV Host Trafficking, Sklan hopes to identify such targets.

“This type of research is not going to offer an immediate remedy, but in the long run it might provide a more efficient approach and be useful for other related viruses as well,” she says.

An estimated 150 million to 200 million people, or around 3% of the world's population, are living with chronic HCV. Approximately 3 to 4 million people are infected each year, usually as a result of blood-to-blood contact, and more than 350 000 people die annually from HCV-related diseases. In the developed world, HCV is the leading cause of costly and complicated liver transplants.

ion of host trafficking machinery by Hepatitis C Virus to promote viral replication
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