Scientists have discovered a cunning strategy used by SARS-CoV-2, the virus that causes Covid-19, to increase its transmissibility.
The team from the Ecole Polytechnique Fédérale de Lausanne (EPFL) in Switzerland focused on the virus’s infamous spike protein, which allows it to enter and infect human cells.
Once SARS-CoV-2 infects a host, it manipulates its cellular machinery, modifying enzymes and accelerating Spike’s ability to invade other cells. This enzyme, abbreviated as ZDHHC20, typically tags proteins with small fatty molecules that change the way they work.
However, upon infection, the virus takes over the ZDHHC20 enzyme, a study published in Nature Communications found.
“In our previous research, we discovered an enzyme that modifies the SARS-CoV-2 spike protein, adding lipids, which is essential for the virus to fuse with target cells,” said EPFL’s Gisou.・Mr. van der Goot said. Faculty of Life Sciences.
“What we now show is that the virus actually causes optimization of the enzyme by inducing changes in the transcription of its genes,” van der Goot added.
Analyzing the effects of SARS-CoV-2 on the gene (zdhhc20), researchers found that the virus causes changes in its transcription start site, the part of the gene where the process of “reading” genes into proteins begins. did.
Studies of both laboratory cells and living organisms confirmed that this “transcriptional change” produced an enzyme with 67 additional amino acids. This is sufficient to increase the lipidation activity upon spiking by 37-fold, leading to a significant enhancement of viral infectivity.
The research team also visualized and quantified the proteins using metabolic labeling, Western blotting, and immunofluorescence to gain a comprehensive picture of the virus’ manipulation tactics.
Digging deeper, the researchers found that this change in gene transcription initiation appears to be something that cells normally make in response to stress or challenge, in the case of this study, chemically induced colitis. discovered.
What this means is that SARS-CoV-2 hijacks existing cell damage response pathways to produce a more infectious virus.
The findings highlight a strategy to increase SARS-CoV-2’s transmissibility and provide a blueprint for potential treatments, while also suggesting that other viruses may use similar strategies to exploit host defenses. It suggests something.
Additionally, the study results indicate that the cellular responses utilized by viruses may be a general response to a variety of stresses, extending the study’s findings beyond viral infections. .