Researchers at Washington State University have uncovered how a group of coronaviruses found in hedgehogs, known as Erinaceus coronaviruses (ErinCoVs), infect host cells. This discovery is a crucial step in understanding the potential of these viruses to move between species and their possible risks to humans. The study, published in Nature Microbiology, found that ErinCoVs are unlikely to infect humans without undergoing multiple genetic changes. However, they may pose more immediate risks to other animals, such as cats. The findings suggest that while the risk to humans is currently low, transmission between hedgehogs and other species could allow the viruses to evolve over time. The researchers identified aminopeptidase N (APN) as the receptor that ErinCoVs use to enter host cells. This is the first time that APN has been shown to be used by a betacoronavirus, the same group that includes the Middle East respiratory syndrome (MERS) virus and SARS-CoV-2, which causes COVID-19. The study involved researchers 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. To understand which species ErinCoVs could potentially infect, the researchers tested versions of APN from about 30 different species. They found that ErinCoVs could not use the human version of APN but were able to use APN from other species, including cats, rats, and elephant shrews. While infections in cats have not yet been confirmed, the study suggests it is biologically possible. Since their first discovery more than a decade ago, ErinCoVs have been found in high numbers of hedgehogs in Europe and Asia. Studies have shown infection rates ranging from about 10% in the United Kingdom to around 60% in Germany and Italy. Although these viruses do not seem to cause serious disease in hedgehogs, their widespread presence increases the chance that they could evolve over time. Scientists have struggled to study ErinCoVs because they cannot be grown in laboratory conditions. To overcome this challenge, the Washington State University-led team used genetic data and laboratory models to recreate harmless but key parts of the viruses, such as their spike proteins, and tested how they interact with cells without using live viruses. Michael Letko, a virologist at Washington State University and senior author of the study, noted that while scientists have known about these viruses for some time, this is the first time they have determined how they infect cells. "That's a crucial step for understanding what they can and can't infect," he said. Victoria Jefferson, a co-first author and postdoctoral fellow in Letko's lab, emphasized that in humans, there are multiple barriers at the receptor level, making it difficult for the virus to enter cells. "Significant mutations would still be needed for the viruses to use human receptors," Jefferson said. Letko added that when viruses can infect multiple species, it is something scientists closely monitor, as each jump into a new host provides the pathogen with more opportunities to evolve and change what it can infect.