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Coronaviruses, already notorious for spilling over into people from various animals and causing new diseases—most catastrophically, COVID-19—may jump into humans even more often than researchers suspected.
Last week, an international collaboration that went looking for known or novel viruses in pneumonia patients in Malaysia reported that in eight children, they found signs of a coronavirus that may have originated in dogs. Earlier this year another group reported a coronavirus that appears to have jumped from pigs to several children in Haiti. There’s no sign so far that either virus can spread from person to person—as the spark of the pandemic, SARS-CoV-2, readily does—or definitive evidence that they cause human illness. But the discoveries, which could increase the number of coronaviruses known to infect people from seven to nine, underscore the threat posed by this viral family.
“I think the more we look, the more we will find that these coronaviruses are crossing species everywhere,” says virologist Stanley Perlman of the University of Iowa.
Malaysian researchers originally partnered with a group at Duke University to study 301 adults and children hospitalized with pneumonia in 2017–18. The eight children with signs of the coronavirus were mainly living in traditional longhouses or villages on Borneo, where they likely had frequent exposure to domestic animals and jungle wildlife. Standard hospital diagnostics for pneumonia or other respiratory illness would not have detected nonhuman coronaviruses, but the Duke team, led by virologist Gregory Gray, had developed a genetic test for conserved coronavirus sequences.
The researchers screened nasopharyngeal samples—secretions and cells swabbed from the upper part of the throat in each patient—and in the children found gene sequences suggesting a novel canine coronavirus. Collaborators from Ohio State University (OSU), Wooster, then cultured virus from one of the children’s samples and sequenced its whole genome. The finding, reported in Clinical Infectious Diseases, is the first report indicating a caninelike coronavirus can replicate in people, and further studies will need to confirm the ability.
The OSU researchers have grown the virus in dog tumor cells, but not yet in human tissue. They are also studying its features, including the spike surface protein that all coronaviruses use to bind to cells and initiate an infection.
The Malaysian children had other virus infections as well, so the coronavirus may not have been the cause of pneumonia. (They all stayed in the hospital for 4 to 6 days and fully recovered.) And each infection may have been a dead-end jump into one person from a nonhuman host, instead of from human-to-human spread. “We don’t have any clear evidence that this particular [coronavirus] strain is better adapted to humans because of its spike structure,” says OSU veterinary virologist Anastasia Vlasova, who led the effort to culture the virus.
Although the genome of the virus overall resembles a canine coronavirus, its spike is closely related to those of canine coronavirus type I and a pig coronavirus known as transmissible gastroenteritis virus. And one key part of the protein bears a 97% similarity to the spike of a coronavirus that infects cats.
This chimera likely arose through multiple genetic swaps between various coronaviruses coinfecting nonhuman hosts. “This is a mosaic of several different recombinations, happening over and over, when nobody’s watching. And then boom, you get this monstrosity,” says virologist Benjamin Neuman at Texas A&M University, College Station. The final host that transmitted the novel virus to the children could have been a cat, pig, dog, “or some wild carnivores,” notes Vito Martella, a veterinary virologist at the University of Bari in Italy.
The genome marks the virus as an alpha coronavirus—the same genus as two coronaviruses that cause common colds. So far, the most dangerous human coronaviruses—those that cause COVID-19 and two other deadly illnesses, severe acute respiratory syndrome and Middle East respiratory syndrome—are in the beta genus. Researchers haven’t seen alphas trigger an outbreak of serious disease in humans, Neuman says, “but that doesn’t feel like much comfort in the wild world of viruses.”
Coronaviruses in another genus may also pose a threat to jump into humans. In March, researchers at the University of Florida reported in a medRxiv preprint the first evidence of a delta coronavirus that infects people, finding signs of a known pig coronavirus in serum from three Haitian children who had fevers in 2014–15. Delta coronaviruses were once thought to infect only birds. Then, in 2012, one infected pigs in Hong Kong. It “appears to have jumped over from songbirds,” says OSU coronavirologist Linda Saif, who grew the virus in swine cell cultures.
Porcine coronaviruses like the ones in Hong Kong and Haiti are a potential epidemic threat, say Ralph Baric of the University of North Carolina, Chapel Hill, and other virologists, because pigs are notorious “mixing vessels” in which viruses can swap genes—the same process that generates new and dangerous strains of influenza. Concern about the virus in Haiti would intensify even more if it was proven to transmit between people, Saif says.
Both studies point to the need for increased vigilance, Baric adds. “This research clearly shows that more studies are desperately needed to evaluate … the frequency of cross-species [coronavirus] transmission and potential for human-to-human spread.”
