Virus co-opts immune protein to avoid antiviral defences

Date:
June 16, 2020
Source:
eLife
Summary:
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 virus infections, according
to new research.



FULL STORY ==========================================================================
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 virus infections, 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
work against all of them, including the SARS-CoV-2 virus causing the
COVID-19 pandemic.

"Previously, clinical trials have shown that blocking CypA reduces the
ability of the hepatitis C virus to replicate and boosts the immune
response," explains lead author Che Colpitts, Assistant Professor of
Biomedical and Molecular Sciences at Queen's University, Kingston,
Canada. "We set out to understand how CypA helps hepatitis C evade the
immune system." In the experiments, the team used hepatitis C-infected
human liver cancer cells with and without a functioning innate immune
system. The innate immune system scans the body for 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 and found
that this stopped the virus from replicating only in the liver cells
with a functioning innate immune system. They also showed that drugs
called cyclophilin inhibitors help block the virus from co-opting CypA
and prevent it from multiplying.

CypA is known to attach to an immune protein called protein kinase R
(PKR), affecting its ability to detect viruses. So, the team used a gene-editing tool called CRISPR/Cas9 to cut out the gene for PKR in
human liver cells with a working innate immune system. In cells without
PKR, the cyclophilin inhibitors were less able to stop the virus from reproducing. This happened because PKR was not there to identify the
virus and trigger antiviral defenses.

"These findings reveal a new antiviral defence mechanism that suppresses
virus growth," says senior author Greg Towers, Professor of Molecular
Virology at University College London, UK. "This opens the door for the development of CypA-targeting antiviral drugs that can be used against
many currently untreatable viruses."

========================================================================== Story Source: Materials provided by eLife. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Che C Colpitts, Sophie Ridewood, Bethany Schneiderman, Justin Warne,
Keisuke Tabata, Caitlin F Ng, Ralf Bartenschlager, David L Selwood,
Greg J Towers. Hepatitis C virus exploits cyclophilin A to evade
PKR. eLife, 2020; 9 DOI: 10.7554/eLife.52237 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/06/200616135808.htm

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