Researchers have now identified a SARS-CoV-2 mutation that drastically affects the ability of the COVID-19 pathogen to infect the central nervous system. These findings may help researchers gain an insight into the neurological symptoms of COVID-19 and the mysterious syndrome called “long COVID,” perhaps opening up doors in the near future for specific treatments designed to protect and clear the brain of the virus.
In a new study, researchers at Northwestern University and the University of Illinois-Chicago identified a set of mutations in the spike protein of SARS-CoV-2 the virus’s exterior component that enables entry into cells which increased the virus’s ability to infect mouse brains.
Their findings were published in the journal Nature Microbiology.
Looking at the genomes of viruses found in the brain compared to the lung, we found that viruses with a specific deletion in spike were much better at infecting the brains of these animals,
This was completely unexpected, but very exciting.
Judd Hultquist
Here the investigators infected mice with SARS-CoV-2 and sequenced the genomes of viruses replicating in the brain versus the lung. In the lung, spike protein had a very close structure to the infecting virus. But inside the brain, most of the viruses bore a deletion or mutation in that critical region of spike that determines entry into a cell. When viruses containing this deletion were used to directly infect the cerebral regions of mice, it was largely restored as it transited to the pulmonary system.
In order for the virus to traffic from the lung to the brain, it required changes in the spike protein that are already known to dictate how the virus gets into different types of cells,
We think this region of spike is a critical regulator of whether or not the virus gets into the brain, and it could have large implications for the treatment and management of neurological symptoms reported by COVID-19 patients.
SARS-CoV-2 has long been associated with various neurological symptoms, such as the loss of smell and taste, “brain fog” and “long COVID.
It’s still not known if long COVID is caused by direct infection of cells in the brain or due to some adverse immune response that persists beyond the infection,
If it is caused by infection of cells in the central nervous system, our study suggests there may be specific treatments that could work better than others in clearing the virus from this compartment.
Judd Hultquist
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Generating new variants in the brain might lead to new variants of concern in the population, said co-corresponding author Justin Richner, assistant professor of microbiology and immunology at UIC.
It could be that the virus is using these different tissue sites to evolve into new, different variants, and then those can traffic back into the respiratory tract and then spread throughout the population,
Potentially this could be a source of novel variants of concern that emerge in the population.
Justin Richner
Source: Northewestern Now
Journal Reference: Class, Jacob, et al. “Evolution of SARS-CoV-2 in the Murine Central Nervous System Drives Viral Diversification.” Nature Microbiology, 2024, pp. 1-12, DOI: https://doi.org/10.1038/s41564-024-01786-8.
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