Human genes involved in COVID-19 infection identified

April 2021 Corona Tobias Rawson

While co-morbidities such as cardiovascular disease and obesity have been linked to worse outcomes in patients infected with COVID-19, research now suggests a biomolecular determinant of COVID-19 prognosis as well. Interferon’s, proteins that can stimulate virus-fighting genes, have been associated with worse clinical outcomes in COVID-19 patients when interferon response to infection is impaired. However, the exact mechanisms that enable COVID-19 cellular invasion to occur, in the setting of impaired interferon activity, is less well defined.

65 genes identified that facilitate covid infection

In an attempt to identify the genes which encode for these mechanisms, a study recently published in Molecular Cell, identified 65 interferon-stimulated genes (ISGs) that mediated COVID-19 host-cell entry and infection. These were primarily genes that encoded for proteins in the endoplasmic recticulum and golgi apparatus that are associated with protein degredation, as well as proteins involved in lipid membrane composition and vesicle transport. Notably, one of the genes identified, BST2, encodes for a protein known to interact with the COVID-19 transmembrane protein Orf7a, enabling viral release into the extracellular space.

“We identified eight ISGs that inhibited both SARS-CoV-1 and CoV-2 replication in the subcellular compartment responsible for protein packaging, suggesting this vulnerable site could be exploited to clear viral infection,” says Laura Martin-Sancho, PhD, first author of the study. “This is important information, but we still need to learn more about the biology of the virus and investigate if genetic variability within these ISGs correlates with COVID-19 severity.”

By identifying these ISGs, it is thought that they could act as therapeutic targets. This idea is further supported by another study, reporting a lower viral load and reduced pulmonary shedding in 127 patients who received interferon beta-1b. Continuing the research further, the research team are currently collecting SARS-CoV-2 variants to understand if the underlying mechanisms of infection differ.

Reference

Martin-Sancho L et al., Functional Landscape of SARS-Cov-2 Cellular Restriction. Molecular cell. 2021. [epub].

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