Recent research has uncovered that viruses, including the one responsible for COVID-19, can induce the fusion of brain cells, leading to malfunction. These findings could potentially shed light on the phenomenon of “brain fog” and other neurological symptoms experienced by some individuals following infection with SARS-CoV-2.
It is widely known that certain viruses, including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have an impact on the brain and nervous system by infecting neurons. Instead of killing the host cells, some viruses prompt brain dysfunction. The mechanism behind this process is well understood in non-brain cells: viruses employ specialized molecules known as fusogens to fuse with and enter cells.
These fusogens take over the cell’s machinery to generate more viruses, spreading the infection, along with additional fusogens, to neighboring cells. However, the effect of fusogens on brain cells has remained unclear until now.
Researchers from Macquarie University in Sydney collaborated with the University of Queensland and the University of Helsinki in Finland to investigate the impact of fusogens on the brain. The study utilized brain organoids, artificially cultivated “mini-brains” that mimic real brain tissue.
Yazi Ke, a co-author of the study, explained, “We reprogram human stem cells into brain cells, including neurons, and allow them to assemble into mini-brains in a dish.”
Some organoids were infected with viral fusogens, including SARS-CoV-2, and were compared with non-infected control organoids. The researchers discovered that the virus triggered fusion not only between neurons but also between neurons and glia, which are non-neuronal cells that support and protect neurons in the brain and spinal cord.
“We discovered COVID-19 causes neurons to undergo a cell fusion process, which has not been seen before,” said Massimo Hilliard, a co-author of the study. “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 a key characteristic of SARS-CoV-2. Located on the virus’s exterior, it enables the virus to invade host cells and initiate infection.
According to the researchers, this fusion process without cell death could potentially explain the persistent neurological symptoms experienced by some individuals after COVID-19 infection, such as headaches, brain fog, loss of taste and smell, and fatigue.
“In the current understanding of what happens when a virus enters the brain, there are two outcomes – either cell death or inflammation,” explained Ramón Martínez-Mármol, the lead author of the study. “But we’ve shown a third possible outcome, which is neuronal fusion.”
This research unveils a novel mechanism underlying the neurological effects following viral infections, enhancing our comprehension of the long-term impacts of COVID-19 and potentially other neurological conditions.
“This comprehensive study can help us understand some of the mechanisms of this viral behavior,” said Lars Ittner, another co-author of the study. “We have also initiated a research program in our laboratory to understand the impact of COVID infections on the brain and how this affects the progression, outcome, and even the onset of dementia.”
The study was published in the journal Science Advances.
Sources: Macquarie University, University of Queensland