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A new study published in Science confirms that SARS-CoV-2 mutated in a way that allowed it to spread rapidly around the world, but the spike mutation could also make the virus more susceptible to a vaccine.
The new coronavirus strain, called D614G, emerged in Europe and has become the most common in the world. Research at the University of North Carolina at Chapel Hill and the University of Wisconsin-Madison shows that the D614G strain replicates faster and is more transmissible than the virus, native to China, which spread at the beginning of the pandemic. .
There were bright spots in the study results: While the D614G strain spreads faster, it was not associated with more severe disease in animal studies, and the strain is slightly more sensitive to neutralization by antibody drugs.
The study released on November 12 provides some of the first concrete results on how SARS-CoV-2 is evolving.
“The D614G virus outstrips and outpaces the ancestral strain by about 10 times and replicates extremely efficiently in primary nasal epithelial cells, which are a potentially important site for person-to-person transmission,” said Ralph Baric, professor of epidemiology at the UNC -Chapel Hill Gillings School of Global Public Health and professor of microbiology and immunology at the UNC School of Medicine.
Baric has been studying coronaviruses for more than three decades and was integral to the development of remdesivir, the first FDA-approved treatment for COVID-19.
Researchers believe that the D614G strain of the coronavirus dominates because it increases the spike protein’s ability to open cells for the virus to enter. These crown-shaped spikes give the coronavirus its name.
The D614G mutation causes a flap to open at the tip of a peak, allowing the virus to infect cells more efficiently, but also creating a path to the vulnerable nucleus of the virus.
With an open flap, it is easier for antibodies, such as those in vaccines currently being tested, to infiltrate and disable the virus.
For the recent study, Baric Lab researchers – including first author Yixuan J. Hou – worked in collaboration with Yoshihiro Kawaoka and Peter Halfmann, both virologists from the University of Wisconsin-Madison faculty.
“The original spike protein had a” D “in this position, and it was replaced by a” G “,” Kawaoka said. “Several papers had already described that this mutation makes the protein more functional and more efficient in entering cells.”
That earlier work, however, relied on a pseudotyped virus that included the receptor-binding protein but was not genuine. Using reverse genetics, Baric’s team replicated a matched pair of mutant SARS-CoV-2 viruses encoding D or G at position 614 and compared basic property analysis using cell lines, primary human respiratory cells, and cells. of mouse and hamster.
Kawaoka and Halfmann contributed to their unique coronavirus study model, which uses hamsters. The University of Wisconsin-Madison team – including Shiho Chiba, who conducted the hamster experiments – performed airborne replication and transmission studies with both the original virus and the mutated version created by Baric and Hou.
They found that the mutated virus not only replicates about 10 times faster, it is also much more contagious.
The hamsters were inoculated with one virus or the other. The next day, eight uninfected hamsters were placed in cages next to the infected hamsters. There was a divider between them so they could not touch each other, but air could pass between the cages.
The researchers began looking for replication of the virus in uninfected animals on the second day. Both viruses passed between animals via airborne transmission, but the times were different.
With the mutant virus, the researchers saw transmission to six out of eight hamsters within two days and to all hamsters by the fourth day. With the original virus, they saw no transmission on day two, although all exposed animals were infected by day four.
“We have seen that the mutant virus transmits better in the air than the [original] virus, which could explain why this virus has dominated in humans, “Kawaoka said.
The researchers also looked at the pathology of the two coronavirus strains. Once infected, the hamsters had essentially the same viral load and symptoms. (Hamsters with the mutated strain lost a little more weight during the illness.) This suggests that while the mutant virus is much better at infecting hosts, it doesn’t cause significantly worse disease.
Researchers warn that the disease findings may not be true in human studies.
“SARS-CoV-2 is a completely new human pathogen and its evolution in human populations is difficult to predict,” Baric said. “New variants are continually emerging, such as the recently discovered SARS-CoV-2 mink cluster 5 variant in Denmark which also codes for D614G.
“To maximize public health protection, we must continue to monitor and understand the consequences of these new mutations on disease severity, transmission, host range and vulnerability to vaccine-induced immunity.”
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