New research has found that viruses such as the one that causes COVID-19 can cause brain cells to fuse together and malfunction. The findings might explain the ‘brain fog’ and other neurological symptoms some people experience following infection with the SARS-Cov-2.
It’s well-known that some viruses, including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, involve the brain and nervous system by infecting nerve cells (neurons).
Some viruses don’t kill their host cells and, instead, cause brain dysfunction. The mechanism by which they do this is understood in non-brain cells: the viruses use specialized molecules called fusogens to fuse with and enter cells. The fusogens hijack the cell's machinery to produce more viruses which spreads the virus – and more fusogens – to neighboring cells. What’s been unclear until now is how fusogens affect brain cells.
Researchers at Macquarie University, Sydney, have collaborated with the University of Queensland and the University of Helsinki, Finland, to examine the effect that fusogens have on the brain. The research relied on brain organoids, artificially grown ‘mini-brains’ that simulate the real thing.
“We reprogram human stem cells into brain cells, including neurons, and allow them to assemble into mini-brains in a dish,” said Yazi Ke, a co-author of the study.
Some organoids were infected with viral fusogens, including SARS-CoV-2, and compared with non-infected control organoids. They found that the virus caused fusion between neurons, between neurons and glia and between glia. Glia are non-neuronal cells in the brain and spinal cord that help support and protect neurons.
“We discovered COVID-19 causes neurons to undergo a cell fusion process, which has not been seen before,” said Massimo Hilliard, one of the study’s co-authors. “After neuronal infection with SARS-CoV-2, the spike S protein becomes present in neurons, and once neurons fuse, they don’t die.”
The spike protein, or S protein, is one of the key biological characteristics of SARS-CoV-2. It’s located on the outside of the virus, allowing it to penetrate host cells and cause infection.
This fusion without cell death, the researchers say, could explain the chronic neurological symptoms some people have after infection with COVID-19, such as headache, ‘brain fog’, loss of taste and smell, and exhaustion.
“In the current understanding of what happens when a virus enters the brain, there are two outcomes – either cell death or inflammation,” said Ramón Martínez-Mármol, lead author of the study. “But we’ve shown a third possible outcome, which is neuronal fusion.”
The research reveals a new mechanism for the neurological events that follow a viral infection which provides a greater understanding of the long-term impacts of COVID-19 and perhaps other neurological conditions.
“This very comprehensive study can help us understand some of the mechanisms of this viral behavior,” said Lars Ittner, one of the study’s co-authors. “We have also started a research program in our lab around understanding the impact of COVID infections on the brain and how this impacts the progression, outcome and even the onset of dementia.”
The study was published in the journal Science Advances.
Sources: Macquarie University, University of Queensland