The hepatitis C virus causes infection to the liver, causing inflammation and could lead to serious damage. It is spread through contaminated blood which an individual may contract in various ways such as the use of an unsterile needle, having HIV, or being born to a mother with hepatitis C. Recently, scientists became interested in how the immune system responds to this virus and compare it to SARS-CoV-2.
Hepatitis C evades the immune system, which led the medical experts to discover a new antiviral defense system that can be applied to various viruses, including coronavirus. One way viruses attack the immune system is by hijacking cellular processes of proteins. The virus attacks healthy cells and multiplies into a new, distorted genetic code of damaged cells.
Other times, viruses with an outer membrane, or enveloped viruses, fuses with healthy, functioning proteins. Vaccinations, such as the vaccine for influenza, have been able to directly target and block the fusion from continuing. Viruses like hepatitis C and all the SARS coronaviruses are known to attack a specific immune protein called cyclophilin A (CypA).
CypA Defense Mechanism
A better understanding of CypA may help international scientists to develop drugs that can target the infected cells of all viruses. Che Colpitts, Assistant Professor of Biomedical and Molecular Sciences at Queen's University, Kingston, Canada said that previous 'clinical trials have shown that blocking CypA reduces the ability of the hepatitis C virus to replicate and boosts the immune response. Colpitts continued, 'we set out to understand how CypA helps hepatitis C evade the immune system."
The study noted, 'One intriguing possibility is that viruses recruit CypA to evade host antiviral responses.' During their experiments, the scientists used human liver cancer cells infected with hepatitis C, which did not include an innate, functioning immune system. The normal response of the human immune system would scan the body for threats, such as a virus or bacteria, and trigger a response.
To mimic this activity, the medical experts used a tool called a short hairpin RNA to specifically target the CypA. They saw how silencing the immune protein stopped the virus from reproducing within the liver cells with a supporting innate immune system. In addition, cyclophilin inhibitors, drugs used to treat hepatitis C, also helped block the virus from attacking CypA and prevented it from multiplying.
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Virus Treatment
CypA attaches to another immune protein, protein kinase R (PKR). Although both acts to protect the body against viral infections, PKR affects CypA's ability to detect viruses. Considering this natural attachment, the scientists used a gene-editing tool called CRISPR/Cas9, cutting 'out the gene for PKR in human liver cells with a working innate immune system.'
Cells without PKR suffered from virus reproduction because the cyclophilin was less able to stop the infection. This is the effect of CypA unable to attach to anything for the virus to be identified and trigger antiviral defenses.
Greg Towers, Professor of Molecular Virology at University College London, UK said, 'These findings reveal a new antiviral defense 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,' including coronavirus.
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