Hedgehog coronaviruses unlikely to infect humans directly, but pose animal transmission risks

Scientists at Washington State University have identified the mechanism by which a family of coronaviruses circulating in hedgehogs breaches the defenses of host cells—a discovery that clarifies both the viruses' capacity to leap between species and their actual threat to human populations. The work, published in Nature Microbiology, offers the first detailed understanding of how these pathogens operate at the cellular level, information that has eluded researchers since the viruses were first documented more than a decade ago.

The viruses in question, called Erinaceus coronaviruses or ErinCoVs, belong to the same family as the pathogen responsible for Middle East respiratory syndrome, a disease that kills roughly one in three people it infects and spreads primarily from camels to humans. That kinship alone has warranted scientific concern. But the new findings suggest the hedgehog viruses pose a different kind of risk—one that may be more immediate for animals than for people. Across Europe and Asia, the viruses have established themselves in hedgehog populations at surprisingly high rates: roughly 10 percent of sampled hedgehogs in the United Kingdom carry them, while infection rates climb to around 60 percent in Germany and Italy. Yet the animals themselves show no signs of serious illness, a fact that has allowed the viruses to circulate widely without triggering obvious alarm.

The research team, led by virologist Michael Letko of WSU's Paul G. Allen School for Global Health, faced a fundamental obstacle: the viruses could not be grown in laboratory conditions, making direct study impossible. Instead, the researchers used genetic data and laboratory models to recreate the spike proteins—the structures that coronaviruses use to unlock their way into cells—and observed how these proteins interacted with cellular machinery. This approach allowed them to work safely while still gathering the information they needed.

What they discovered was that ErinCoVs rely on a receptor called aminopeptidase N, or APN, to gain entry into host cells. This finding itself was novel: it marked the first time this particular receptor had been shown to serve as an entry point for any betacoronavirus, the group that includes both MERS and SARS-CoV-2. The team then tested versions of APN from roughly thirty different species to map where the viruses could successfully establish infection. The results were telling. The human version of APN proved incompatible with the hedgehog viruses—they could not use it to enter human cells. But the viruses could use APN from several other species: cats, rats, and elephant shrews, small African mammals.

This selective compatibility matters because it reveals a potential pathway for viral evolution. When a virus jumps into a new host species, it gains opportunities to accumulate genetic changes that might eventually alter what it can infect. The researchers emphasized that significant mutations would still be required before these viruses could threaten humans. Victoria Jefferson, a co-first author on the study, noted that human cells present multiple barriers at the receptor level—structural differences that make it substantially harder for the virus to breach the cellular membrane. But the ability to infect cats and other animals creates a biological scenario worth monitoring.

In regions where hedgehogs and cats coexist, the animals interact frequently enough that transmission between species is plausible, even though confirmed infections in cats have not yet been documented. Each such transmission event would give the virus another chance to mutate, to adapt, to potentially shift its capabilities. The research team, which drew collaborators from ten institutions worldwide including Yale University, the National Institutes of Health's Vaccine Research Center, and the University of Toronto, has mapped the immediate risk landscape: low for humans in the near term, but contingent on continued surveillance and on understanding how these viruses might evolve as they move through animal populations.