by Sara Lidman, Karolinska Institutet

SARS-CoV-2 infection inhibited SGs formation independent of eIF2α. Credit: Nature Communications (2024). DOI: 10.1038/s41467-024-54996-3

Researchers at Karolinska Institutet have discovered how the SARS-CoV-2 virus, which causes COVID-19, manipulates human proteins to replicate and evade the immune system. The results have been published in Nature Communications.

The new study shows that SARS-CoV-2 uses human proteins called G3BP to increase its replication. One of the virus’s proteins binds to G3BP and prevents the formation of so-called stress granules, which would otherwise have an antiviral effect.

“Our research shows that SARS-CoV-2 reprograms the G3BP proteins to facilitate its RNA replication while simultaneously suppressing the cell’s defense mechanisms,” says Siwen Long, first author, and doctoral student in Molecular Virology at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet.

Identifying G3BP’s critical role in supporting the replication of SARS-CoV-2 opens new possibilities for antiviral therapies. Previous research has shown that hijacking G3BP is crucial for other viral infections, such as alphavirus and norovirus.

“This means that targeted treatments against this interaction could potentially treat a wide range of viral infections,” says Long.

The researchers studied the role of the G3BP protein in the virus’s replication by creating a mutant virus variant called RATA, which cannot bind to G3BP. In infections with the RATA variant, the protective stress granules persist longer, reducing the virus’s replication and significantly weakening the severity of the disease in a mouse model.

“Our future research will focus on understanding the molecular mechanisms in detail and finding strategies to selectively disrupt G3BP’s interaction with viral proteins without affecting its normal function in cells,” says Gerald McInerney, Professor of Molecular Virology at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet.

More information: Siwen Long et al, SARS-CoV-2 N protein recruits G3BP to double membrane vesicles to promote translation of viral mRNAs, Nature Communications (2024). DOI: 10.1038/s41467-024-54996-3

Journal information:Nature Communications

Provided by Karolinska Institutet

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