London: Scientists from Trinity College Dublin have discovered how the highly infectious and sometimes deadly hepatitis C virus (HCV) “ghosts” our immune system and remains undiagnosed in many people. They report their findings today in the international FASEB journal.
HCV’s main route of transmission is via infected blood, but over the past 40 years, it has accidentally been given to many patients across the world via contaminated blood products. The virus replicates particularly well in the liver, and the damage it causes makes it a leading cause of liver disease worldwide.
Even though HCV can be deadly, initial infection is rarely accompanied by any apparent clinical symptoms for reasons that have—until now—remained unknown. As a result, it often goes undiagnosed for the first 6-12 months following infection.
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If left untreated HCV spreads throughout the liver, stimulating a low-level inflammatory response. Over several months, these mild responses—accompanied by subsequent liver repair—result in fibrotic scarring of the liver. The liver’s main job is to filter out toxins, but during HCV infection, the build-up of fibrotic, non-functioning liver tissue, results in 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 realize they are infected with HCV, their first noticeable symptoms are the side-effects of liver fibrosis (such as jaundice).
While the majority of HCV infections are now treatable with new medicines, early detection would avoid the damaging progression to liver disease. Therefore, a group of scientists led by Assistant Professor in Immunology at Trinity, Nigel Stevenson, set out to understand how the virus avoids being discovered for months after infection.
HCV suppresses the immune response: Indeed, they have found that HCV has developed multiple strategies to suppress the immune system.
Under normal circumstances, our cells communicate with each other with molecules called cytokines, which work by activating specific cascades of different particles within our cells called signaling pathways. These cytokines and their signaling pathways trigger the expression of hundreds of molecules within our cells to increase inflammation and anti-viral activity. This immune response is capable of killing and clearing the viral infection for our cells and bodies.
Uncontrolled inflammation would be dangerous, however, so to ensure our immune response to infection is appropriately regulated; several cytokine signaling pathways are controlled by immune regulators called “suppressor of cytokine signaling (SOCS).” After some time following an initial response, pro-inflammatory cytokine signaling pathways are shut down by SOCS.
The Trinity scientists found that HCV “ghosts” our immune response, by triggering our own SOCS regulators; a specific part of the virus is responsible for increasing a specific SOCS molecule—in both liver and immune cells.