Scientists have discovered a mutation in SARS-CoV-2, the virus that causes COVID-19, that plays a key role in its ability to infect the central nervous system. The findings may help scientists understand its neurological symptoms and the mystery of “long COVID,” and they could one day even lead to specific treatments to protect and clear the virus from the brain.

The new collaborative study between scientists at Northwestern University and the University of Illinois-Chicago uncovered a series of mutations in the SARS-CoV-2 spike protein (the outer part of the virus that helps it penetrate cells) that enhanced the virus’ ability to infect the brains of mice.

“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,” said co-corresponding author Judd Hultquist, assistant professor of medicine (infectious diseases) and microbiology-immunology at Northwestern University Feinberg School of Medicine. “This was completely unexpected, but very exciting.”

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In this study, researchers infected mice with SARS-CoV-2 and sequenced the genomes of viruses that replicated in the brain versus the lung. In the lung, the spike protein looked very similar to the virus used to infect the mice. In the brain, however, most viruses had a deletion or mutation in a critical region of spike that dictates how it enters a cell. When viruses with this deletion were used to directly infect the brains of mice, it was largely repaired when it traveled to the lungs.

“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,” Hultquist said. “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,” Hultquist said. “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.”

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Materials provided by Northwestern University. Note: Content may be edited for style and length.

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Journal Reference:

1. Jacob Class, Lacy M. Simons, Ramon Lorenzo-Redondo, Jazmin Galván Achi, Laura Cooper, Tanushree Dangi, Pablo Penaloza-MacMaster, Egon A. Ozer, Sarah E. Lutz, Lijun Rong, Judd F. Hultquist, Justin M. Richner. Evolution of SARS-CoV-2 in the murine central nervous system drives viral diversification. Nature Microbiology, 2024; DOI: 10.1038/s41564-024-01786-8

Source: Spike mutations help SARS-CoV-2 infect the brain | ScienceDaily

The elimination of damaged cell components is essential for the maintenance of the body’s tissues and organs. An international research team led by the University of Bonn has made significant findings on mechanisms for the clearing of cellular wastes, showing that strength training activates such mechanisms. The findings could form the basis for new therapies for heart failure and nerve diseases, and even afford benefits for manned space missions.

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he protein BAG3 plays a critical role in the elimination of damaged components, identifying these and ensuring that they are enclosed by cellular membranes to form an “autophagosome.” Autophagosomes are like a garbage bag in which cellular waste is collected for later shredding and recycling. The research team led by Professor Jörg Höhfeld of the University of Bonn Institute of Cell Biology has shown that strength training activates BAG3 in the muscles.

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“Impairment of the BAG3 system does indeed cause swiftly progressing muscle weakness in children as well as heart failure — one of the most common causes of death in industrialized Western nations,”

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: “We now know what intensity level of strength training it takes to activate the BAG3 system, so we can optimize training programs for top athletes and help physical therapy patients build muscle better.”

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“BAG3 is activated under mechanical force. But what happens if mechanical stimulation does not take place? In astronauts living in a weightless environment, for example, or immobilized intensive care patients on ventilation?” In such cases, the lack of mechanical stimulation rapidly leads to muscle atrophy, the cause of which Höhfeld ascribes at least in part to the non-activation of BAG3. Drugs developed to activate BAG3 might help in such situations, he believes

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Story Source:

Materials provided by University of Bonn. Note: Content may be edited for style and length.

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Journal Reference:

1. Judith Ottensmeyer, Alessandra Esch, Henrique Baeta, Sandro Sieger, Yamini Gupta, Maximilian F. Rathmann, Andreas Jeschke, Daniel Jacko, Kirill Schaaf, Thorsten Schiffer, Bahareh Rahimi, Lukas Lövenich, Angela Sisto, Peter F.M. van der Ven, Dieter O. Fürst, Albert Haas, Wilhelm Bloch, Sebastian Gehlert, Bernd Hoffmann, Vincent Timmerman, Pitter F. Huesgen, Jörg Höhfeld. Force-induced dephosphorylation activates the cochaperone BAG3 to coordinate protein homeostasis and membrane traffic. Current Biology, 2024; DOI: 10.1016/j.cub.2024.07.088

Source: Strength training activates cellular waste disposal | ScienceDaily