In a groundbreaking study, scientists from Ecole Polytechnique Federale de Lausanne (EPFL) in Switzerland have uncovered a sophisticated strategy employed by SARS-CoV-2, the virus responsible for Covid-19, to increase its infectivity. The focus of their research was on the virus’s spike protein, a notorious component that facilitates its entry and infection of human cells.
The study reveals that upon infecting a host, SARS-CoV-2 takes control of an enzyme called ZDHHC20, which typically tags proteins with a small fat molecule, altering their functionality. This manipulation turbocharges the spike protein’s ability to invade other cells, enhancing the virus’s overall infectivity.
Gisou van der Goot, from EPFL’s School of Life Sciences, explains, “In our previous work, we discovered the enzyme that modifies the SARS-CoV-2 spike protein — it adds lipids to it — and this is essential for the virus to fuse with target cells. What we now show is that the virus actually triggers an optimization of the enzyme by inducing a change in the transcription of its gene.”
Further analysis of the virus’s impact on the gene zdhhc20 revealed a change in its transcriptional start site, the segment of a gene where the process of “reading” it into a protein begins. This alteration results in an enzyme with 67 additional amino acids, significantly boosting its lipid-adding activity on the spike protein by 37 times.
The researchers used various techniques, including metabolic labeling, Western blotting, and immunofluorescence, to visualize and quantify proteins, gaining a comprehensive understanding of the virus’s manipulative tactics.
Digging deeper, the scientists found that the change in the transcriptional start of genes mirrors a response cells typically exhibit in the face of stresses or challenges. This suggests that SARS-CoV-2 co-opts a pre-existing cell damage response pathway to generate more infectious viruses.
This groundbreaking discovery not only sheds light on the tactics employed by SARS-CoV-2 to enhance its infectivity but also provides a blueprint for potential treatments. Moreover, it suggests that other viruses might employ similar strategies by co-opting host defenses. The findings also indicate that the cellular response the virus leverages could be a general reaction to various stresses, expanding the study’s relevance beyond viral infection.
