A team of scientists has produced an infectious form of the hepatitis virus for the first time in the laboratory. What's so important about that? They say it allows medical experts to study every stage of the hepatitis C (HCV) life cycle and develop new medications to treat the disease.
Their experiment is reported in the June 9 issue of Science magazine.1
"The inability to reproduce aspects of the hepatitis C virus life cycle in cell culture has slowed research progress on this important human pathogen [disease-causing organism]," said chief investigator Charles Rice, PhD, who heads the Laboratory of Virology and Infectious Disease at Rockefeller University.
Risk Factors and Symptoms
Hepatitis C infection is a disease of the liver caused by the hepatitis C virus. Those at risk include the following people:
• Those who received blood from a donor who later tested positive for HCV infection.
• Those who have injected illegal drugs, even many years ago.
• Those who received a blood transfusion or solid organ transplant before 1992.
• Those were recipients of clotting factors before 1987.
• Those who have ever been on long-term kidney dialysis.
• Those who have evidence of liver disease, such as persistently high levels of a liver enzyme called alanine aminotransferase (ALT).
Signs and symptoms of hepatitis C infection include the following:
• Jaundice
• Fatigue
• Dark urine
• Abdominal pain
• Loss of appetite
• Nausea
The number of new infections per year has plunged from about 240,000 in the 1980s to about 30,000 in 2003. However, nearly 4 million Americans are infected with the viral disease, of whom about 2.7 million are chronically infected.2
Unveiling New Knowledge About HCV
According to experts, hepatitis C cannot replicate (make copies of itself) by itself. It must first infect cells in the body, and use the cells' infrastructure to successfully make copies of itself.3 However, up until now, little has been understood about the life cycle of the hepatitis C virus because medical researchers haven't been able to reproduce an infectious form of the virus that they can observe in cell cultures.
"This system lays the foundation for future test tube studies of the virus life cycle, and may help in the development of new drugs for combating HCV," Rice said, in explaining the lab experiment that he and his colleagues described in their study paper.
How HCV Infects Cells
Based on research on the life cycle of hepatitis C, researchers believe the virus enters a liver cell, and delivers its genetic material, as well as certain proteins, into the cell's cytoplasm.4 According to experts, the virus separates its genetic component from the proteins it releases, copies that genetic component, then joins with new genetic component with the protein. This new, copied form of the virus is released from the liver cell to invade other liver cells.
"The hallmark of viruses is their ability to exist in a form outside the host cell capable of infecting new cells," said study researcher Brett Lindenbach, PhD, a postdoctoral fellow in Rice's lab. "Our method replicates and produces virus particles that can infect new cells, initiating replication in them and leading to the production of more virus particles."
In other words, Rice's group managed to create the same process in a lab experiment as what is seen in the human body during the onset of infection.
A Molecule Friendly to HCV
The research team named their infectious cell culture HCVcc, and already, it's giving them new knowledge about the biology of HCV. In a separate set of experiments, Rice and his team used HCVcc to confirm that a certain molecule, which sits on the surface of human cells, mediates the entry of the hepatitis C virus into the cells.
It's long been known that a protein produced by the hepatitis C virus binds to this molecule,5 and it's believed this interaction is necessary for the virus to bind to targeted liver cells.
In this study, Rice's group found that forms of the molecule that do not sit on the surface of cells compete with those that do, and prevent HCV from entering the cell.
In conclusion, the research team wrote: "HCVcc replication was inhibited by interferon-alpha and by several HCV-specific antiviral compounds, suggesting that this in-vitro system will aid in the search for improved antivirals."
1. Lindenbach BD, Evans MJ, Syder AJ et al. Complete replication of hepatitis C virus in cell culture. Science 2005 Jul 22;309(5734):623-6. Epub 2005 Jun 9.
2. Centers for Disease Control and Prevention. Viral Hepatitis C. Available at: http://www.cdc.gov/ncidod/diseases/hepatitis/c/fact.htm.
3. Moriishi K, Matsurra Y. Mechanisms of hepatitis C virus infection. Antivi Chem Chemother 2003 Nov;14(6):285-97.
4. Chang M, Williams O, Mittler J et al. Dynamics of hepatitis C virus replication in human liver. Am J Pathol 2003 Aug;163(2):433-4.
5. Machida K, Cheng KT, Pavio N, Sung VM, Lai MM. Hepatitis C virus E2-CD81 interaction induces hypermutation of the immunoglobulin gene in B cells. J Virol 2005 Jul;79(13):8079-89.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include overseeing health news coverage for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
