Body's immune response drives production of non-functional coronavirus 'gateway protein': Study

London, October 25

Some immune system molecules trigger the production of a non-functional variant of the human protein used by the novel coronavirus to enter and infect host cells, according to a study that sheds light on the body’s natural defence against COVID-19.

The research, published in the journal Nature Genetics, examined the genetic information that codes for the ACE2 receptor, to which the SARS-CoV-2 virus must bind in order to enter and infect human cells.

In the study, scientists, including those from the Francis Crick Institute in London, analysed existing genetic databases and human cells to identify a new variant, or isoform, of ACE2 called MIRb-ACE2, which the SARS-CoV-2 virus cannot bind to.

“This variant of genetic information is the result of retroelements in our DNA, which can ‘jump’ around the genome impacting gene expression,” said Kevin Ng, a co-author of the study from the Francis Crick Insitute.

“From looking at which other species also have this variant, it appears to be widely present in mammals, so it must have entered the human genome a long time ago,” he added.

In order to understand the role this variant plays in the body’s immune response to SARS-CoV-2, the scientists assessed the effects of exposing cells to interferons — signalling proteins that are made and released by virus-infected cells.

They found that interferons increase the response and production specifically of MIRb-ACE2, while ACE2 is not affected.

According to the researchers, the findings allay concerns that interferon-based treatments for SARS-CoV-2 could inadvertently be helping the virus by bringing about an increase in coronavirus cell receptors in the body.

They said the coronavirus is not able to bind to MIRb-ACE2, which is also highly unstable.

“The non-functional MIRb-ACE2 isoform was likely responsible for results from previous studies that suggested interferons could be upregulating ACE2, as there was no distinction between these two isoforms,” said George Kassiotis, another co-author of the study.

“This highlights how scientific knowledge about SARS-CoV-2 is constantly being revised and updated as new research is carried out. We still have a lot to learn, but we are making rapid progress,” Kassiotis said.

The researchers also found that cells in the upper aero-digestive tract, including the mouth and the nose, express more MIRb-ACE2 than the functional ACE2, and this balance changes lower in this tract and in the intestines.  

They believe more research is needed to understand why this difference occurs and the impact it might have on how the virus spreads in the body. PTI