Raccoon dogs, depicted here on a fur farm in China’s Hebei Province, are susceptible to SARS-CoV-2 and were sold at various markets in Wuhan.Credit: Greg Baker / AFP through Getty
SARS-CoV-2, the virus that causes COVID-19, may have been spilled from animals into humans several times, according to a preliminary analysis of viral genomes sampled from infected people in China and elsewhere early in the year. pandemic.
If confirmed by additional analysis, the findings would increase the weight of the hypothesis that the pandemic originated in several Wuhan markets and would make the hypothesis that SARS-VOC-2 escaped from a laboratory less likely, according to some researchers. . But the data needs to be verified and the analysis has not yet been peer-reviewed.
The first viral sequences, taken from infected people in late 2019 and early 2020, are divided into two major lineages, known as A and B, that show key genetic differences.
Lineage B has become the dominant lineage worldwide and includes samples taken from people who visited the Huanan Seafood Market in Wuhan, which also sold wild animals. Lineage Spread in China and includes samples of people linked to other Wuhan markets.
A crucial question is how the two viral lineages relate. If lineage A viruses evolved from lineage B viruses or vice versa, this would suggest that the progenitor of the virus once jumped from animals to humans. But if the two lineages have separate origins, there may have been multiple derivative events.
Dagger in the heart
The latest analysis, posted on the virological.org discussion forum, adds weight to the second possibility by questioning the existence of genomes that link lineages.
The finding could be the “dagger to the heart” of the hypothesis that SARS-CoV-2 escaped from a laboratory, rather than coming from the wildlife trade, says Robert Garry, a virologist at Tulane University in Nova Orleans, Louisiana. But others say more research is needed, especially given the limited genomic data from the onset of the pandemic.
“It’s a very significant study,” Garry says. “If you can show that A and B are two separate lineages and there were two side effects, it all eliminates the idea that it came from a lab.”
The results are “consistent with there being at least two introductions of SARS-CoV-2 into the human population,” says David Robertson, a virologist at the University of Glasgow, UK.
Lineages A and B are defined by two key nucleotide differences. But some of the early genomes have a combination of these differences. The researchers previously thought that these genomes could be those of viruses in intermediate stages of evolution that unite the two lineages.
But the researchers behind the new analysis looked at them in detail and noticed some problems.
Fine tooth comb
They analyzed 1,716 SARS-CoV-2 genomes in a popular online genome repository called GISAID that were collected before February 28, 2020 and identified 38 “intermediate” genomes.
But when they examined the sequences more closely, they found that many of these also contained mutations in other regions of their genome. And they say that these mutations are definitely associated with lineage A or lineage B, which discredits the idea that the corresponding viral genomes date from an intermediate stage of evolution between the two lineages.
The authors suggest that a laboratory or computer error in the sequencing of one of the two mutations in these “intermediate” genomes probably occurred. “The more we dug, the more it seemed, maybe we can’t trust any of the‘ transitional ’genomes,” says study co-author Michael Worobey, an evolutionary biologist at the University of Arizona in Tucson.
These sequencing errors are not unusual, the researchers say. Sometimes software can fill gaps in raw data with incorrect sequences and viral samples can become contaminated, notes Richard Neher, a computer biologist at the University of Basel in Switzerland. “These setbacks are not surprising,” he says. “Especially in the early days of the pandemic, when protocols weren’t very established and people were trying to generate data as quickly as possible.”
Several researchers contacted Nature, who sequenced some of the samples included in the study, say their sequences are unlikely to include errors in the two key nucleotides. But the study’s authors counter that even if some of the genomes were sequenced correctly, other parts of the same genome or the locations from which the samples were collected still clearly indicate that they belong to only one or the other. lineage, he says.
“It’s very unlikely” that any of the so-called intermediate genomes are actually transition genomes, according to study co-author Joel Wertheim, a molecular epidemiologist at the University of California at San Diego.
Xiaowei Jiang, an evolutionary biologist at Xi’an Jiaotong University-Liverpool in Suzhou, China, says the team behind the study must verify the results by obtaining “the original raw sequencing data for as many genomes as possible. possible “.
Many markets
If the virus jumped between animals and people on several occasions, the fact that lineages A and B are related to people who visited different markets in Wuhan suggests that several individual animals, of one or more species, carrying a parent of SARS- CoV-2 could have been transported through Wuhan, infecting people in at least two places.
A study published in June1 they found that live animals susceptible to SARS-CoV-2, such as raccoon and mink dogs, were sold in numerous markets in Wuhan. Previous studies2 of the virus that caused the severe acute respiratory syndrome (SARS) have concluded that it probably also jumped several times from animals to people.
The latest study, if verified, would mean that the scenario of a researcher accidentally infected in a lab and then spreading the virus to the general population should have happened twice, Garry says. According to him, the pandemic is much more likely to have its origins in the wildlife trade.
To gather more evidence, the team behind the new analysis now plans to perform computer simulations to test the extent to which multiple spills were adapted to the diversity of known SARS-CoV-2 genomes.