How hepatitis C 'ghosts' immune system

Discovery by Trinity scientists
  • Deborah Condon

Scientists in Trinity College Dublin (TCD) have discovered how the highly infectious hepatitis C virus is able to ‘ghost' the immune system, remaining initially undiagnosed in people for many months.

The hepatitis C virus affects the liver, causing inflammation and scarring (fibrosis) of the liver tissue. It is one of the leading causes of liver disease worldwide.

The main way that the virus is transmitted is via infected blood. Over the last four decades, it has accidentally been given to many patients worldwide as a result of infected blood products.

The virus can be deadly, but when a person is initially infected, they may not have any obvious symptoms. As a result, the condition can often go undiagnosed for six to 12 months following infection. If patients are not aware they have the virus, their first noticeable symptoms tend to be the side-effects of liver fibrosis, such as jaundice.

While most hepatitis C infections can be treated with medicines, early detection would avoid the damaging progression to liver disease. The TCD scientists set out to determine how the virus avoids being detected for months after infection.

Under normal circumstances, our cells communicate with each other with molecules called cytokines, which work by activating other molecules within our cells called signalling pathways. These cytokines and their signalling pathways work to increase inflammation and antiviral activity. This immune response is capable of killing and clearing viral infections from our cells and bodies.

However, uncontrolled inflammation is dangerous, so to ensure our immune response to infection is appropriately regulated, several cytokine signalling pathways are controlled by immune regulators called suppressor of cytokine signalling (SOCS) regulators. After a period of time following an initial response, pro-inflammatory cytokine signalling pathways are shut down by SOCS.

The scientists found that the hepatitis C virus ‘ghosts' our immune response, by triggering our own SOCS regulators in both liver and immune cells. In fact, a specific part of the virus is responsible for increasing a specific SOCS molecule.

"We've discovered that the virus hijacks this regulatory process by causing the expression of SOCS in our cells. By increasing the expression of SOCS, the virus basically dulls the normal immune response to viral infection. Without a strong signal, our body's cells cannot then mount an effective inflammatory and antiviral response that clears infection," explained lead scientist and assistant professor in immunology at TCD, Dr Nigel Stevenson.

He said that this ability ‘shields' the hepatitis C virus from the body's normally effective antiviral immune response, creating ‘a perfect environment in which to survive, replicate and infect other cells'.

"Many diseases are mediated by increasing the inflammatory response to an inappropriately high level, but in this case it is the lack of adequate inflammation that enables HCV to go undiagnosed, leaving it free to rapidly replicate and infect other cells," Dr Stevenson added.

Details of these findings are published in the The FASEB (Federation of American Societies for Experimental Biology) Journal.

 


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