“No evidence supports this,” says Vincent Racaniello, Columbia University virologist and author of an article in which he demonstrates that the study published in Cell don’t bring any evidence increased human transmission of this mutant SARS-CoV-2 strain. First of all, the experiments carried out in this study were carried out on a “pseudotyped” virus, which means that the researchers did not use the real SARS-CoV-2 virus. In order to prove that the mutation increases transmissibility, it would have been necessary to observe the behavior of the authentic mutant in human subjects.
“There is a huge gap between laboratory infectivity and human transmission,” says Nathan Grubaugh, epidemiologist and virologist attached to Yale University. In the real world, he explains, a virus has to make its way to the lungs by passing through the mucus and immune cells that line the airways. It must then replicate and survive in the droplets released into the air. The scenario described in the review Cell is plausible, Grubaugh says, but “there are so many variables to consider. “
So how much should we worry about coronavirus mutations? Here are the answers to National Geograpghic from prominent virologists and doctors.
MUTATION G614, SITUATION
The authors of the study published in Cell, under the direction of biologist Bette Korber of the national laboratory of Los Alamos in New Mexico, cut / pasted the protein Spike (S), a protein in the shape of a spike also called peplomer, of the mutant version (G614) or original coronavirus on a completely independent germ called lentivirus.
As Korber explains to us, the “pseudoviruses” thus obtained make it possible to manipulate and compare different viral peaks in a safe and reproducible manner.
The team of researchers then introduced these pseudoviruses into test tubes to mix them with different types of liver cells, a batch taken from Vervet monkeys 60 years ago and another from humans in 1973. These cells also been immortalized, on the famous model of cellules d’Henrietta Lacks. This means that they have been modified naturally or artificially to live forever, unlike the cells in the human body. In addition, the human cells used in Korber’s study have been genetically altered to be more easily infected by any virus carrying the Spike protein.
In this artificial scenario, in vitro, the researchers did find that the mutant Spike protein was more infectious. Add to this the fact that the dominance of the G614 mutation has been established in the space of a few months, and you get a virus with an already frightening profile whose ability to jump from one individual to another seems to have improved . It didn’t take more for the media to catch fire.
But then, what do the results of the study mean as they stand today?
“We don’t know,” replied Racaniello simply. Even though experiments using pseudoviruses are a common practice in virology, it’s a bit like putting tiger teeth in the mouth of a koala. Even if the bite of the mutant koala will be more painful, experience tells you nothing about the ferocity of koalas or tigers outside the laboratory.
Korber recognizes the limits of the experimental results: “We don’t know” how this will translate into transmissibility between humans, she admits, but “this point is currently being studied in several laboratories. “
In the meantime, there is another explanation for the lightning spread of the virus among the population and its dominant role in the pandemic, an explanation which leaves aside the G614 mutation in itself.
THE FOUNDING EFFECT
During their replication, viruses can mutate, each cycle being assimilated to a roll of genetic dice. Many of these mutations will not offer any benefit, but will still be transmitted until they become frequent in a population. This phenomenon is called the “founding effect”.
The G614 mutation has been identified for first time in China in January 2020, when the new coronavirus broke into Europe. This suggests that the global domination of this mutant strain could only be due to its presence at the beginning of the European epidemic, the gateway to the virus in the rest of the Western world. By integrating the founding effect into a recent analysis of the coronavirus genomes collected from 23,000 patients worldwide, the Genetics Institute at University College London could only note the absence of evidence of increased transmissibility of current SARS-CoV-2 mutations, including G614.
Although Korber acknowledges the plausibility of the founding effect, she considers that the frank prevalence of G614 worldwide implies that the mutation confers a functional advantage on the virus and, according to her, the evidence suggests that the mutant strain surpass the original strain. “Almost every time, out of the dozens and dozens of situations where the two forms were circulating in an area, the virus ended up adopting the G614 form more frequently,” she says.
However, another group of independent researchers, the COVID-19 Genomics UK consortium, follows the evolution of the G614 mutation in British patients and has analyzed to date more than 30,000 viral genomes. While the G614 mutation “is potentially at the origin of an increase in the rate of transmission between individuals, the difference that we observe is much less pronounced than the difference in cellular infectious power measured in the laboratory,” we read in the communicated addressed by Erik Volz, epidemiologist at Imperial College London and member of the consortium.
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