A new study published in the journal Cell reports the effects of a genetic mutation in SARS-CoV-2, the virus responsible for COVID-19. Conducted by researchers from Los Alamos National Laboratory, Duke University and the University of Sheffield in the U.K., it suggests that a variation in SARS-CoV-2’s genome improved the virus's ability to infect human cells and helped it become the dominant strain circulating globally.
The coronavirus variant – named D614G – has a genetic “glitch” in the spike protein, which it uses to gain access to human cells. An earlier study from the Scripps Research Institute in Florida associated the variation with increased viral transmissions, making the virus more infectious in vitro. (Related: Coronavirus research: “Mutated” virus now more infectious than ever.)
“The D614G variant first came to our attention in early April, as we had observed a strikingly repetitive pattern,” explained Dr. Bette Korber, a theoretical biologist at Los Alamos and the study’s lead author.
“All over the world, even when local epidemics had many cases of the original form circulating, soon after the D614G variant was introduced into a region, it became the prevalent form.”
A controversial variant
The D614G variant of the coronavirus is a hot topic among scientists. For some experts, the gene variation in D614G increased its “contagiousness” by improving the virus’s ability to attach to cells. This could also explain why the variant is now seen in around 70 percent of samples in Europe and North America.
However, not everyone agrees that the mutation played a role in the variant’s spread. Other experts argue that a more likely explanation is that D164G spread widely by chance, mainly from explosive outbreaks in Europe.
The issue has become so controversial that even Dr. Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases, has acknowledged the dispute.
“The data is showing there’s a single mutation that makes the virus be able to replicate better and maybe have high viral loads,” Fauci said in a JAMA Network interview. However, he noted that the presence of a gene variation does not necessarily mean a person infected by it will have poorer outcomes than those infected by the original.
“It just seems that the virus replicates better and may be more transmissible,” he added.
In the new study, the researchers looked at genome samples published on GISAID, a global repository used by researchers to share genomic data from viruses, including SARS-CoV-2. This allowed the team to track how the D614G variant upended the original SARS-CoV-2 based on geographic samples that included data from countries and cities.
“The consistency of this pattern was highly statistically significant, suggesting that the D614G variant may have a fitness advantage,” the researchers wrote in their report.
The team also included two lines of experimental evidence that supported initial findings. In particular, the additional experiments showed how the mutations found in D614G increased its infectivity in vitro. Together with clinical data, more extensive sequencing and improved statistical models, this finding supports the idea that D614G is a more transmissible virus.
On the other hand, the researchers highlighted the need for more in vivo studies to determine the full implications of the genetic variation in D614G, acknowledging the possibility of alternative explanations.
“It’s exciting to see a group take on the challenge of solving this, and the differences they report are intriguing, particularly the consistency across geography,” said Dr. Marc Suchard, a biostatistician at the David Geffen School of Medicine at UCLA. “But this is an extraordinarily challenging problem, the evolution and demography are complex, so there’s much more work to be done.”
Sources include:
Cell.com [PDF]
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