By discovering a trick the hepatitis C virus uses to evade the immune system, scientists have identified a new antiviral defence system that could be used to treat many viruses, according to new research published today in eLife.
Viruses have many strategies to avoid immune system defenses. They often do this by hijacking the immune system’s own proteins. One immune protein that is frequently targeted by viruses, including HIV, hepatitis C, and the SARS coronavirus, is called cyclophilin A (CypA). Understanding how CypA is used by viruses could help scientists develop drugs that works against all of them, including the SARS-CoV-2 virus causing the COVID-19 pandemic.
In the experiments, the team used hepatitis C-infected human liver cancer cells with and without a functional innate immune system, which detects potential threats such as viruses or bacteria and triggers a response. The scientists used a tool called a short–hairpin RNA to selectively silence CypA, or CypA-targeting drugs called cyclophilin inhibitors, and found that this stopped the virus from replicating only in the liver cells with a functional innate immune system. In the absence of CypA, the virus was detected by the innate immune system, which then stopped the virus from reproducing. In contrast, in the cells without a functional immune system, the cyclophilin inhibitors were less able to stop the virus from replicating.
These findings identify a new antiviral approach that acts by harnessing the power of the body’s innate immune system and may be effective against many currently untreatable viruses.
“Previously, clinical trials have shown that blocking CypA reduces the ability of the hepatitis C virus to replicate and boosts the immune response. We set out to understand how CypA helps hepatitis C evade the immune system.”
– Lead author Che Colpitts, Assistant Professor of Molecular Virology in the Department of Biomedical and Molecular Sciences at Queen’s University
“These findings reveal a new antiviral defence mechanism that suppresses virus growth. This opens the door for the development of CypA-targeting antiviral drugs that can be used against many currently untreatable viruses.”
– Greg Towers, Professor of Molecular Virology at University College London, UK