Hundreds of mammal species can serve as coronavirus incubators to mix and match with each other, potentially forming new viruses and feeding the future pandemics, foresees a new study. These species include wild animals, such as bats and monkeys, as well as domestic animals, such as pigs and cats.
The study, published on February 16 in the journal Nature Communications, highlights the potential for coronavirus to infect a wide range of hosts. In fact, the work identifies hundreds of animal species that can be infected with known coronaviruses, although many of these infections have not yet been seen in the wild.
Coronaviruses are a large family of viruses that can infect birds and mammals; SARS-CoV-2, the virus that causes COVID-19, is just one member of the coronavirus family. For the research, the team designed the genetic sequences for 411 coronavirus from GenBank, a database from the National Institutes of Health, and tracked those sequences using a computer algorithm. The sequences represented 92 different species of coronavirus, with some species represented by more than one strain of virus.
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The algorithm predicted that, on average, each virus has more than 12 mammalian hosts. Each species of animal screened, in turn, was predicted to be a potential host for more than five coronaviruses, on average.
Animals that can serve as hosts for many coronaviruses pose the greatest threat; when multiple strains of coronavirus invade the same cell, their genes can be mixed and matched as they replicate, thus generating a new patchwork virus.
It is genetic Card shuffling, known as “recombination,” can be especially dangerous if SARS-CoV-2 exchanges genes with another coronavirus, the authors wrote. That’s because the resulting virus could potentially be just as infectious to humans as SARS-CoV-2, but it could perhaps invade additional tissues or cause more serious illness. The model identified 126 non-human species that could host SARS-CoV-2 and at least one other coronavirus, which could allow this worrying scenario to develop.
“More surprising than any individual animal was the wide range of animals that are expected to host a large number of coronaviruses,” wrote study authors Maya Wardeh, a data scientist, and Marcus Blagrove, a virologist at the University of Liverpool, in England, in a joint statement to Live Science. “Everybody knows it bats are important, but we found many high-risk hosts in all mammals, including rodents, primates [and] hoofed animals. “
That said, just because two coronaviruses can invade the same animal doesn’t mean they can and will recombine, said Arinjay Banerjee, a virologist at McMaster University in Ontario who was not involved in the study. Recombination requires viruses to enter the same cell type and infections to peak at the same time, among other logistics, he said. But the new study provides a useful list of mammal species that should be monitored for coronavirus infections and recombination events in the future, he said.
A potential infection network
To predict which mammals are likely hosts for coronavirus, the authors created a computer algorithm that mapped the connections between potential hosts and known coronaviruses. The algorithm analyzed known coronaviruses and observed which animals they infect. He then examined other closely related animals, lived in similar habitats or ate the same types of diet, as they were likely to be suspected of harboring similar populations of coronavirus. The algorithm also compared the genome sequences of different coronaviruses, with the idea that closely related coronaviruses are likely to be able to infect similar hosts.
After finding these connections, the algorithm identified which mammals could potentially harbor many coronaviruses and therefore be the focus of coronavirus recombination.
The team tracked 876 species of mammals using this algorithm, including 185 known coronavirus hosts. The remaining 691 species belonged to the same genus as a known host. The algorithm tested potential links between these animals and the 411 coronaviruses for which the RNA sequence is already known.
“These 411 viruses contain all seven coronaviruses known to infect humans, as well as the full range of other coronaviruses whose genomes have been sequenced,” said the authors.
Although all sequenced strains of SARS-CoV-2 were included in the analysis, they were treated as a single entity in the analysis. “The SARS-CoV-2 variants are all very similar, with only relatively minor mutations; we do not expect our results for host specificity to be very different between them,” the authors told Live Science.
Of the 126 species identified as potential hosts for SARS-CoV-2, several animals stood out for presenting the greatest risk of recombination. Some of these animals have already been signaled as potential recombination hosts for SARS-CoV-2, as well as for the SARS-CoV-related virus, which caused outbreaks of severe acute respiratory syndrome in the early 2000s.
For example, the Asian civet (Paradoxurus hermaphroditus) was a predicted host for 32 coronaviruses, in addition to SARS-CoV-2. The larger horseshoe bat (Rhinolophus ferrumequinum) and intermediate horseshoe bat (Rhinolophus affinis) were predicted hosts for 67 and 44 additional coronaviruses, respectively, and the pangolin (Manis javanica) by 14.
In addition to these suspicious hosts, the model highlighted wild animals that were not previously associated with the SARS-CoV-2 recombination. These included the smaller Asian yellow bat (Scotophilus kuhlii), chimpanzee (Pan troglodytes) and African green monkey (Chlorocebus aethiops) The common hedgehog (Erinaceus europaeus), European Bunny (Oryctolagus cuniculus) and domestic cat (Felis catus) are also likely hosts for coinfection and recombination, the model predicted.
But the “most prominent result for a SARS-CoV-2 recombination host is the domestic pig (Sus scrofa), “planned to house 121 coronaviruses in addition to SARS-CoV-2, wrote the authors.
“Given the large number of coronaviruses that our structure predicts that pigs can be infected, we suggest monitoring pigs at ‘high risk’ [living conditions]”the authors told Live Science. For example, pigs kept in rooms close to other high-risk farm animals would be considered high risk, while pigs kept isolated from other animals would be relatively low risk, they said.
High-risk scenarios
The study also identified 102 potential species that could be co-infected with SARS-CoV-2 and MERS-CoV, the coronavirus that causes Middle East Respiratory Syndrome (MERS). MERS has a lethality rate much higher than COVID-19, estimated at about 35%, so the recombination of these two viruses can be extremely dangerous, making the resulting virus highly transmissible and susceptible to causing serious illness, the authors said.
The model also predicted possible interactions that did not include SARS-CoV-2. The team found that many genetically diverse coronaviruses may be able to mix and exchange their RNA; for example, 291 mammal species were predicted hosts of coronaviruses of four or more different subgenera, a taxonomic subcategory below the genus and above the species.
However, coronaviruses of the same subgenus are more likely to recombine than viruses of different subgenera, Banerjee said. “We don’t know if different subgenres would recombine; it’s unlikely, but it hasn’t been demonstrated experimentally,” he said.
The domestic pig, the smaller Asian yellow bat and the larger and intermediate horseshoe bats emerged as likely hosts for these recombination events, but other species also appeared on the high-risk list. Notably, this included the dromedary camel (Camelus dromedarius), a well-known coronavirus host and the main transmitter of MERS-CoV to humans.
Looking ahead, the study authors plan to develop a similar model for bird species, to see which birds can be a source of coronavirus recombination; known avian coronavirus hosts include turkey (Meleagris gallopavo) and guinea fowl (Numida meleagris), among others, according to a 2005 report in Avian Pathology. After collecting data on birds, the team wants to model the frequency with which potential coronavirus hosts across the animal kingdom come into contact with each other.
“This will allow estimates of where within the geographic area a host species is most at risk and thus direct surveillance more specifically to ‘what and where’,” said the authors. In addition, they plan to incorporate clinically relevant data into their predictions, addressing which viruses are known to cause disease in humans and what type of symptoms they trigger.
For now, the likelihood of recombination in different species is uncertain, as is the risk that these theoretical mash-ups could make people sick, Banerjee said. But “my conclusion from this manuscript is [to] to extend surveillance to under-studied and underestimated potential reservoirs of coronaviruses, “said Banerjee. A species of reservoir would carry coronaviruses without becoming ill, but then pass the viruses on to other animals that became ill; bats are a large reservoir of coronaviruses, for example.
This early identification of potential hosts for coronavirus could help scientists develop surveillance programs aimed at detecting recombination “as it is happening and before a major outbreak,” the authors wrote. And in the event of an outbreak, scientists could easily consult the record of coronaviruses found in high-risk animals to identify the new pathogen, Banerjee said.
Originally published on Live Science.