Trinity researchers, led by Dr Nigel Stevenson, an assistant professor in immunology, have discovered how the Hepatitis C virus “ghosts” the immune system by triggering a suppressor of an immune regulator.
Hepatitis C, which is highly infectious and can be deadly, is mainly transmitted through infected blood and replicates well in the liver, resulting in liver disease. Despite these potentially sinister effects, initial infection is rarely accompanied by any obvious clinical symptoms for reasons that have – until now – remained unknown. As a result, it often goes undiagnosed for the first 6 to 12 months following infection.
If left untreated, the virus spreads throughout the liver, stimulating a low-level inflammatory response. Over several months, this results in fibrotic scarring of the liver and reduced liver function. Without a fully functioning liver, one major side effect is the build-up of toxins, often referred to as “jaundice”. If patients do not realise they are infected with Hepatitis C, this is one of the first noticeable symptoms. While the majority of Hepatitis C infections are now treatable with new medicines, early detection would avoid the damaging progression to liver disease.
Under normal circumstances, our cells communicate with each other using a domino-effect chain of multiple molecules that make up signalling pathways. They trigger our cells to increase inflammation and antiviral activity. This immune response is capable of killing and clearing viral infections from our cells and bodies.
Uncontrolled inflammation would be dangerous, however, so these pathways are controlled by immune regulators called “Suppressor Of Cytokine Signalling” regulators. After a period of time following an initial response, pro-inflammatory signalling pathways are shut down by the immune regulators. Stevenson’s team found that Hepatitis C “ghosts” our immune response, by triggering our own suppressor of cytokine signalling regulators, in both liver and immune cells.
In a press statement, Stevenson said: “We’ve discovered that HCV [Hepatitis C virus] hijacks this regulatory process by causing the expression of SOCS [Suppressor Of Cytokine Signalling] in our cells. By increasing the expression of SOCS, HCV basically dulls the normal immune response to viral infection. Without a strong signal our body’s cells cannot then mount an effective inflammatory and anti-viral response that clears infection.”
“This ability shields HCV from our body’s normal, effective anti-viral immune response and creates 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.”