‘Crazy interesting’ findings by Australian researchers may reveal key to Covid immunity

Australian researchers have found a protein in the lungs that sticks to the Covid-19 virus like velcro and immobilises it, which may explain why some people never become sick with the virus while others suffer serious illness.

The research was led by Greg Neely, a professor of functional genomics with the University of Sydney's Charles Perkins Centre in collaboration with Dr Lipin Loo, a postdoctoral researcher and Matthew Waller, a PhD student. Their findings were published in the journal PLOS Biology on Friday.

The team used human cells in tissue culture to search the whole human genome for proteins that can bind to Sars-CoV-2, the virus which causes Covid-19.

This was done using the genetic engineering tool known as Crispr, which allowed them to turn on all genes in the human genome, then look to see which of those genes give human cells the ability to bind to the Sars-CoV-2 spike protein. The spike protein is crucial to the virus's ability to infect human cells.

"This let us find this new receptor protein, LRRC15," Neely said.

"We then used lungs from patients that died of Covid or other illnesses and found the serious Covid patients had tons of this LRRC15 in their lungs."

LRRC15 is not present in humans until Sars-CoV-2 enters the body. It appears to be part of a new immune barrier that helps protect from serious Covid-19 infection while activating the body's antiviral response.

Despite those patients who died from Covid-19 producing LRRC15, the researchers believe not enough was produced to be protective, or it was produced too late to help.

"When we look at lungs from patients that died of Covid there is much of this protein," Neely said. "But we couldn't look at the lungs of patients that survived Covid as lung biopsy is not something that is easy to do on live people. We predict there is more of this protein in survivors versus those that died of Covid."

A separate study from London that examined blood samples for LRRC15 found the protein in the blood was lower in patients with severe covid compared to patients that had mild Covid, supporting this theory.

"Our data suggests that higher levels of LRRC15 would result in people having less severe disease," Neely said.

"The fact that there's this natural immune receptor that we didn't know about, that's lining our lungs and blocks and controls virus - that's crazy interesting."

They also found LRRC15 is also expressed in fibroblast cells, the cells that control lung fibrosis, a disease which causes damaged and scarred lung tissue. Covid-19 can lead to lung fibrosis, and the finding may have implications for long Covid.

"We can now use this new receptor to design broad-acting drugs that can block viral infection or even suppress lung fibrosis," Neely said. There are currently no good treatments for lung fibrosis, he said.

Loo said LRRC15 "acts a bit like molecular velcro, in that it sticks to the spike of the virus and then pulls it away from the target cell types".

Prof Stuart Turville, a virologist with the Kirby Institute at the University of New South Wales, said the finding is "a powerful example" of what happens when teams work together in Australia.

"Greg Neely's team is brilliant at what we call functional genomics," Turville said.

"That is the ability to wake up or turn off thousands of proteins at a time and when looking at new viruses, this is really important. Our team provided the platforms and virus for testing in this setting and these collaborations are really powerful both now and also in the future for emerging pathogens."

And while the discovery may take years to translate into drugs that can protect against viruses and other diseases, Turville said the research adds to our understanding of innate immunity - hard-wired responses humans have that can act as soon as a virus appears.

"Understanding these pathways is important as they enable us to put the brakes on a virus, so other arms of our immune system can catch up and respond," Turville said.

"In some cases these brakes can be so effective, that the virus may never gain momentum. Indeed this could be one of many factors that may increase the ability of people to be protected from the virus early on."