This protein, the leucine-rich repeat-containing protein 15 (LRRC15), is an inbuilt receptor that binds the SARS-CoV-2 virus without passing on the infection.
The research opens up an entirely new area of immunology research around LRRC15 and offers a promising pathway to develop new drugs to prevent viral infection from coronaviruses like COVID-19 or deal with fibrosis in the lungs.
The study has been published in the journal PLOS Biology. It was led by Professor Greg Neely with his team members Dr Lipin Loo, a postdoctoral researcher, and PhD student Matthew Waller at the Charles Perkins Centre and the School of Life and Environmental Sciences.
The University study is one of three independent papers that reveal this specific protein’s interaction with COVID-19.
“Alongside two other groups, one at Oxford, the other at Brown and Yale in the USA, we found a new receptor in the LRRC15 protein that can stop SARS-CoV-2. We found that this new receptor acts by binding to the virus and sequestering it which reduces infection,” Professor Neely said.
“For me, as an immunologist, 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.
“We can now use this new receptor to design broad acting drugs that can block viral infection or even suppress lung fibrosis.”
What is LRRC15?
The COVID-19 virus infects humans by using a spike protein to attach to a specific receptor in our cells. It primarily uses a protein called the angiotensin-converting enzyme 2 (ACE2) receptor to enter human cells. Lung cells have high levels of ACE2 receptors, which is why the COVID-19 virus often causes severe problems in this organ of infected people.
Like ACE2, LRRC15 is a receptor for coronavirus, meaning the virus can bind to it. But unlike ACE2, LRRC15 does not support infection. It can, however, stick to the virus and immobilise it. In the process, it prevents other vulnerable cells from becoming infected.
“We think it acts a bit like Velcro, molecular Velcro, in that it sticks to the spike of the virus and then pulls it away from the target cell types,” Dr Loo said.
“Basically, the virus is coated in the other part of the Velcro, and while it's trying to get to the main receptor, it can get caught up in this mesh of LRRC15,” Mr Waller said.
LRRC15 is present in many locations such as lungs, skin, tongue, fibroblasts, placenta and lymph nodes. But the researchers found human lungs light up with LRRC15 after infection.
“When we stain the lungs of healthy tissue, we don't see much of LRRC15, but then in COVID-19 lungs, we see much more of the protein,” Dr Loo said.
“We think this newly identified protein could be part of our body’s natural response to combating the infection creating a barrier that physically separates the virus from our lung cells most sensitive to COVID-19.”