Hepatitis C virus found to spread directly from cell to cell by-passing antibodies

Nov 5 2007

Scientists looking for an effective treatment for Hepatitis C may face an even bigger task than anticipated. Recent studies looking into how the virus spreads in liver tumour cells have demonstrated that the virus uses two different routes, which may explain why the body's natural occurring antibodies are ineffective at controlling the virus.

The Medical Research Council funded McKeating laboratory, based at the Institute for Biomedical Research at the University of Birmingham, has discovered that the virus does not need to be released by a cell before infecting the next one, but can slip directly from one to the other and avoid the body's neutralizing antibodies or medical attempts to boost antibody production. They have also found that the direct cell-to-cell route can transmit virus infectivity independently of a co-receptor molecule called CD81, previously reported to be essential for extracellular virus infection of a cell.

Hepatitis C virus (HCV) affects 170 million individuals worldwide. At present the only approved treatment is interferon which is toxic and only effective in 50 per ct of cases. The race to find an effective treatment is on and many scientists and pharmaceutical companies are interested in compounds that block virus interaction with the CD81 co-receptor as a way of stopping viral spread. This discovery may come as a setback to those existing efforts to develop new drugs to target the disease.

Jennifer Timpe, the lead author on the paper who presented the study at the recent 14th International Symposium on Hepatitis C Virus in Glasgow, explains: “Viruses can spread by two different mechanisms: via extracellular virus particles or direct cell-to-cell transfer. Until now, HCV was thought to spread by extracellular viruses infecting cells, a route vulnerable to antibodies. But our research shows the virus to uses both mechanisms to get around. This is probably why it has been so tricky to tackle.” These latest results seem to indicate, from laboratory tests, that the virus' dramatic spread in acute Hep C cases may result from cell-to-cell transfer which appears to be a faster mechanism for the virus to infect new target cells. Jennifer Timpe concludes “Finding that Hep C uses multiple mechanisms for spreading around the body was not great news, but this discovery will allow those of us working in this area to move ahead with a better understanding of the virus. We will have to up our game and find other ways of tackling this relentless virus. Future studies will investigate the pathways of cell-cell transfer of infectivity which may reveal new targets for antiviral therapy.”