Scientists discover how hepatitis C "alters" our immune system

Scientists at Trinity College Dublin have discovered how hepatitis C virus (HCV), highly infectious and sometimes deadly, "ghosts" our immune system and remains undiagnosed in many people. Today, they report on their discoveries at the international level. FASEB Journal.

The main route of HCV transmission is infected blood, but in the last 40 years it has been accidentally administered to many patients around the world via infected blood products. The virus replicates particularly well in the liver and the damage it causes makes it one of the leading causes of liver disease in the world.

Although HCV can be fatal, the initial infection is rarely accompanied by obvious clinical symptoms for reasons that have remained unknown until now. As a result, it often remains undiagnosed for 6 to 12 months after infection.

If it is not treated, HCV spreads throughout the liver, stimulating a low-level inflammatory response. Over several months, these mild responses – accompanied by subsequent repair of the liver – result in fibrous scarring of the liver. The main task of the liver is to filter toxins, but during HCV infection, the formation of nonfunctional fibrotic liver tissue results in a reduction in liver function.

Without a fully functional liver, one of the major side effects is the formation of toxins, often referred to as "jaundice". If patients do not realize that 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 can now be treated with new drugs, early detection would prevent the adverse progression of liver disease. Therefore, a group of scientists led by Nigel Stevenson, assistant professor of immunology at Trinity, sought to understand how the virus avoids being discovered for months after infection.

HCV suppresses the immune response

Indeed, they found that HCV had developed multiple strategies to suppress the immune system.

Under normal circumstances, our cells communicate with each other with molecules called cytokines, which activate specific cascades of other molecules within our cells, called signaling pathways. These cytokines and their signaling pathways trigger the expression of hundreds of molecules in our cells in order to increase inflammation and antiviral activity. This immune response is able to kill and eliminate the viral infection for our cells and our body.

Uncontrolled inflammation, however, would be dangerous. Therefore, to ensure proper regulation of our immune response to infection, several cytokine signaling pathways are controlled by immune regulators called "cytokine signaling inhibitors (SOCS)". After a period of time following an initial response, the pro-inflammatory cytokine signaling pathways are closed by SOCS.

Trinity scientists have discovered that HCV "ghosts" our immune response by triggering our own SOCS regulators; a specific part of the virus is responsible for the increase of a specific SOCS molecule, both in liver and immune cells.

Dr. Stevenson said:

"We have discovered that HCV is diverting this regulatory process by causing the expression of SOCS in our cells.In increasing the expression of SOCS, HCV attenuates the normal immune response to viral infection. Without a strong signal, our body's cells could only have an effective inflammatory and antiviral response that eliminates the infection.

This ability protects HCV from our body's normal and effective anti-viral immune response and creates an ideal environment for surviving, replicating and infecting other cells. Many diseases are mediated by increasing the inflammatory response to an excessively high level, but in this case, it is the lack of adequate inflammation that allows the HCV to be undiagnosed, allowing it to replicate quickly and effectively. infect other cells. "