BySHIRA SILKOFF
Updated:

Could the coronavirus Omicron variant have evolved in mice? New research indicates that the highly infectious SARS-CoV-2 variant known as Omicron may have jumped ship from humans to animals, and then back again.

The two prevailing theories to explain Omicron

A peer-reviewed study titled “Evidence for a mouse origin of the SARS-CoV-2 Omicron variant,” published in last month’s issue of the Journal of Genetics and Genomics looked at the rapid accumulation of mutations in the Omicron variant and attempted to understand how and why the virus acquired the mutations it did in the length of time it did.


The Omicron mutation was first detected by South African scientists on November 24, 2021, and was classified as a variant of interest by the World Health Organization, primarily due to its rapid spread and a high number of unusual mutations.


While two prevailing theories already existed among scientists to explain how exactly Omicron developed, a team of researchers at the Chinese Academy of Sciences in Beijing found evidence of a third theory that suggests Omicron may have mutated and evolved in mice.


The first theory as to how Omicron evolved so extensively without being detected until November hypothesizes that it could have spread cryptically, developing and mutating in a population with insufficient viral surveillance and sequencing technology. In this case, it could have spread undetected until it reached South Africa, where advanced technology picked up on it. However, researchers have suggested that this scenario is highly unlikely, as intermediate steps in Omicron’s evolution should still have been picked up from people traveling between countries.


Test tubes labelled ''COVID-19 Omicron variant test positive'' are seen in this illustration picture taken January 15, 2022.
Test tubes labelled ''COVID-19 Omicron variant test positive'' are seen in this illustration picture taken January 15, 2022. (credit: REUTERS/DADO RUVIC/ILLUSTRATION)


The second hypothesis suggests that Omicron could have developed in a single person, a chronically infected patient who provided a suitable host environment for the virus to mutate and adapt over an extended period of time. This phenomenon has been observed before in chronic COVID-19 patients with compromised immune systems, although never to the extent seen in Omicron, which has accumulated over 50 mutations.

A third hypothesis emerges



Dissatisfied with both these options, the Beijing research team set out to investigate the possibility of a third option, one that theorized that an earlier mutation transferred from humans to mice sometime during 2020, mutated quietly as it spread among mice for over a year, before transferring back to humans toward the end of 2021.

Since the start of the pandemic, SARS-CoV-2 has proven multiple times that it is able to spread to other species with relative ease. It has been detected in cats and dogs, hyenas and hippopotamuses, in ferrets and hamsters, and even in a wild leopard. In fact, millions of mink were culled in farms across Europe in 2020 after the virus was found to be circulating among the species. So it is not beyond the realm of imagination to suggest that it could have jumped to mice at any point over the last two years.

In order to prove their hypothesis, the research team identified the mutations acquired by Omicron before its outbreak and tested whether or not the molecular spectrum of the mutations was consistent with the cellular environment of human hosts.

According to previous studies conducted by the same team, many mutated RNA virus genomes tend to pick up more mutations in particular bases, according to which species they are replicating inside. This means that the virus genomes are dependent on species-specific processes and mechanisms in order to divide and evolve, and as a result, specific mutation types will be highly prevalent depending on the species in which the virus has evolved.


Coronavirus (illustrative).
Coronavirus (illustrative). (credit: PIXABAY)


In this case, when testing the pre-outbreak Omicron mutations, the research team found prominent dissimilarities between the molecular spectrum of Omicron and the molecular spectrum of multiple different variants known to have evolved in humans, including those of three variants that evolved in chronic COVID-19 patients.

Therefore, the molecular structure of Omicron was inconsistent with the standard molecular spectrum of variants that had developed in humans.


In light of this finding, the scientists sought to determine which nonhuman host species could have been accountable for the virus mutations. To do this, they retrieved 17 sequences of murine (mice) hepatitis viruses, 13 canine coronaviruses, 54 feline coronaviruses, 23 bovine (cattle) coronaviruses, and 110 porcine (pig) Delta coronaviruses.


The research team then worked to compare the molecular spectrum of Omicron with the molecular spectra of these sequences, using molecular docking-based analyses to investigate whether the Omicron spike protein mutations could be associated with adaptations made by the virus in other host species. And indeed, the researchers found that the mutations in the Omicron spike protein had significant overlap with mutations in mouse-adapted SARS-CoV-2.

Discovery of variants that could infect mice



Several of the Omicron mutations allowed the coronavirus variant to bind tightly to mice and rats but would not have been as effective when it came to binding to humans, making it highly unlikely that they developed anywhere but in rodents. While originally at the start of the pandemic, mice had been reported to be poor hosts for the virus, as different variants emerged several succeeded in infecting mice. For example, variants harboring the specific spike mutation N501Y were relatively common in human patients, but they were also able to infect mice, potentially allowing the disease to jump from human to mouse and spread among the rodent species.

Once the jump from human to mouse had been made, the infection could then have spread freely among mice, evolving and adapting independently, even as other variants such as Delta continued to spread through humans, until an opportunity arose for the then thoroughly mutated mouse variant to jump back into the human species.
Furthermore, the research suggested, while evolving in mice, the virus developed mutations associated with immune escape, accounting for its rapid spread in humans.

A mouse, illustrative image. (credit: INGIMAGE)


This study, the research team emphasized, highlights “the need for viral surveillance and sequencing in animals, especially those in close contact with humans.” This is because humans are the largest known group of carriers of SARS-CoV-2, and frequently come into contact with other animals, be it pets, wild animals, or livestock.
“Given the ability of SARS-CoV-2 to jump across various species, it appears likely that global populations will face additional animal-derived variants until the pandemic is well under control,” the study concluded.