PULLMAN, Wash. — Washington State University researchers have discovered how a group of coronaviruses circulating in hedgehogs invades host cells, a key to understanding their potential to jump between species and their risk of causing a pandemic in humans.
Known as Erinaceus coronaviruses, or ErinCoVs, the viruses have concerned scientists because of their close relation to the one that causes Middle East respiratory syndrome, or MERS, a severe respiratory disease that spreads mainly from camels to humans and kills about one-third of infected people. The researchers found the hedgehog viruses are unlikely to infect humans without first undergoing multiple genetic mutations, but they may pose more immediate risks to other animals, including cats. The findings were published in Nature Microbiology.
"Scientists have been aware of these viruses for a while, but for the first time, we were able to figure out how they infect cells," said Michael Letko, a virologist in the WSU College of Veterinary Medicine's Paul G. Allen School for Global Health and senior author of the study. "That's a crucial step for understanding what they can and can't infect."
Since first being detected more than a decade ago, the viruses have been found in high numbers of sampled hedgehogs in Europe and Asia, with studies finding infections in anywhere from about 10% in the United Kingdom to around 60% in Germany and Italy. The viruses don't appear to cause serious disease in hedgehogs, but their widespread circulation increases the chances they could evolve over time.
Scientists have struggled to study the viruses because they have been unable to grow them in laboratory conditions. Using genetic data and laboratory models, the WSU-led team was able to recreate harmless but key parts of the viruses – like their spike proteins – and test how they interact with cells, without working with live viruses.
Like other coronaviruses, ErinCoVs rely on spike proteins to attach to receptors on the surface of host cells. The researchers identified aminopeptidase N, or APN, as the receptor used by the viruses to gain entry. It is the first time the receptor has been shown to be used by a betacoronavirus, the same group that includes MERS and SARS-CoV-2, the strain of coronavirus that causes COVID-19.
Once the receptor was identified, researchers tested versions of APN from about 30 species to see where the viruses could gain entry. They found the viruses could not use the human version of APN, but they were able to use APN from a small number of other species, including cats, rats and elephant shrews – mouse-sized mammals native to Africa.
"When we see viruses that can get into multiple species, that's something we pay attention to," Letko said. "Each jump into a new host gives the pathogen more opportunities to pick up mutations that could change what it can infect."
Significant mutations would still be needed for the viruses to use human receptors.
"In humans, there are multiple barriers at that receptor level," said Victoria Jefferson, a co-first author on the study and a postdoctoral fellow studying in Letko's Laboratory of Functional Viromics. "Those differences make it much harder for the virus to enter cells."
While the risk to humans remains low, Letko and Jefferson said transmission between hedgehogs and other animal species could give the viruses opportunities to adapt over time. Cats could represent one possible pathway. In regions where hedgehogs are common, the animals frequently interact, creating opportunities for transmission. While infections in cats have not been confirmed, the findings suggest it is biologically plausible.
The study involved collaborators from 10 institutions worldwide, including Yale University, the National Institutes of Health's Vaccine Research Center, the University of Toronto and several research institutes in Italy.
