New research has identified a range of mutations in the spike protein of the SARS-CoV-2 virus that improve its ability to infect the brains of mice. These discoveries may help researchers better understand the neurological symptoms associated with COVID-19 and the enigma of ‘long COVID.’ In the future, they might even lead to targeted treatments aimed at protecting the brain and eliminating the virus from it.
Researchers have pinpointed a mutation in the SARS-CoV-2 virus, which is responsible for COVID-19, that significantly impacts its capacity to invade the central nervous system. This research could provide insights into the neurological issues linked to the virus and the phenomenon of “long COVID,” potentially paving the way for specialized therapies to safeguard and eradicate the virus in the brain.
A joint research effort by scientists from Northwestern University and the University of Illinois-Chicago has revealed several mutations in the SARS-CoV-2 spike protein. This protein, found on the virus’s surface, is crucial for its entry into cells, and these mutations have enhanced the virus’s ability to infect mouse brains.
“By comparing the genetic structures of viruses found in the brain with those in the lung, we discovered that viruses harboring a specific deletion in the spike protein were significantly more effective at infecting the brains of these mice,” explained co-corresponding author Judd Hultquist, who is an assistant professor of medicine (infectious diseases) and microbiology-immunology at Northwestern University Feinberg School of Medicine. “This finding was entirely unexpected and very thrilling.”
The findings of this study will appear in the upcoming edition of Nature Microbiology on August 23.
Modifications in the spike enhance the virus’s ability to infect different cells
In their study, researchers infected mice with SARS-CoV-2 and sequenced the viruses that multiplied in the brain versus those in the lung. While the spike protein in lung samples closely resembled the virus that infected the mice, most brain viruses exhibited either a deletion or mutation in a crucial part of the spike protein responsible for cell entry. When the brain-infecting viruses were used to infect mice directly, the mutations were mostly repaired when the virus moved to the lungs.
“For the virus to migrate from the lung to the brain, it required alterations in the spike protein known to influence how the virus enters various cell types,” Hultquist said. “We believe this particular region of the spike protein is essential in determining whether the virus can access the brain, which could significantly affect how neurological symptoms in COVID-19 patients are treated and managed.”
SARS-CoV-2 has been linked to a variety of neurological symptoms, including the loss of smell and taste, cognitive difficulties commonly referred to as “brain fog,” and the phenomena associated with “long COVID.”
“It’s still unclear whether long COVID results from a direct attack on brain cells by the virus or due to an adverse immune response that lingers after the infection,” Hultquist noted. “Should it be a result of the brain’s cells being infected, our research implies there could be particular treatments that may outperform others in eliminating the virus from this area.”
Other contributors from Northwestern University include Lacy M. Simons, Tanushree Dangi, Egon A. Ozer, Pablo Penaloza-MacMaster, and Ramon Lorenzo-Redondo.
This study, titled “Evolution of SARS-CoV-2 in the murine central nervous system drives viral diversification,” received funding from several sources including the National Institutes of Health (grants R01AI150672; R56DE033249; R21AI163912; and U19AI135964), the Department of Defense (grant MS200290), and institutional support from the Center for Pathogen Genomics and Microbial Evolution as well as the Northwestern University Clinical & Translational Sciences Institute (NUCATS).
