Key change in genetics of SARS-CoV-2 evolved to counter weakness caused by the virus’ initial mutation that enabled its spread
Researchers at Johns Hopkins Medicine say their new studies suggest that the first pandemic-accelerating mutation in the SARS-CoV-2 virus, which causes COVID-19, evolved as a way to correct vulnerabilities caused by the mutation that started the SARS-CoV-2 pandemic.
The new evidence, published in the Dec. 23 issue of Science Advances, addresses important biological questions about two key mutations in the virus’ surface “spike” protein, say the researchers. It suggests that a mutation called D614G in the gene for the spike protein, which arose just a few months after the virus started to spread in human populations, was not an adaptation to its new human host. Rather, the mutation was an adaptation to the dramatic changes that happened in the spike gene just before the start of the pandemic, which allowed SARS-CoV-2 to spread between people by respiratory transmission.
Research by other scientists across the world has shown that this mutation enabled the virus’ spike protein to be cut and primed it for rapid infection of cells lining the airway.
Soon after the pandemic began, in early 2020, researchers from the University of Toronto discovered a subsequent SARS-CoV-2 mutation, called D614G; however, its precise function was not known.
Working with dozens of blood samples from patients with COVID hospitalized in April 2020 at The Johns Hopkins Hospital, the team isolated antibodies for the spike protein from the patients’ blood samples. Then, they used these antibodies to track the location of spike proteins in human cells genetically engineered to produce the spiky surface molecules.
They found that the D614G mutation redirects the spike protein and pulls the virus from the surface of human cells into a tiny compartment within the cell called a lysosome, which the spike protein reprograms into storage containers that are used to release infectious virus particles from the cell.
In addition, the D614G mutation caused a three-fold drop in the abundance of spike proteins at the cell surface.
