Merbecoviruses, closely related to the Middle East respiratory syndrome coronavirus, circulate in hedgehogs throughout Europe and Asia, raising concerns about zoonotic transmission to humans and domestic animals. However, it is not clear how these viruses enter host cells. Here we tested three coronavirus receptors from European hedgehogs (Erinaceus europaeus) in cell-based assays and identified aminopeptidase N (APN) as a receptor for hedgehog merbecoviruses. We verified it by pseudotype experiments using an in vitro reporter system based on replication competent vesicular stomatitis virus and protein binding assays. Hedgehog coronavirus spike proteins showed enhanced infectivity when produced at 33 °C, approximating the physiological hedgehog body temperature, as compared with 37 °C. A screen of 30 mammalian APN orthologues showed restricted cross-species receptor use, including the inability to use human APN. Electron cryomicroscopy revealed a distinct glycoprotein-receptor interface unlike known coronavirus spike-APN interactions, clarifying species barriers. These findings broaden our understanding of receptor use across merbecoviruses and betacoronaviruses and inform risk assessments for viral emergence.
M. Jin, Victoria A. Jefferson, Zhe Zhao et al.· Nature Microbiology· 0 citations
Virus exposure history, particularly first exposure, is believed to shape vaccine efficacy and infection susceptibility; however, evidence for mechanistic links between immune responses in individuals and epidemiological outcome in populations is scarce. Recent co-circulation of SARS-CoV-2 variants XFG and BA.3.2 has revealed a striking enrichment in BA.3.2 cases among children. By combining epidemiological modeling, serology and monoclonal antibody analysis in children and adults, we show the dependence of effective variant-specific antibodies on vaccination history which may explain birth-year influence on differential susceptibility to these co-circulating variants. Ancestral cross-reactive site I antibodies frequently neutralize BA.3.2, but not XFG. By contrast, Omicron type-specific site I/III and III antibodies frequently neutralize XFG but not BA.3.2, revealing a tradeoff in the ability to neutralize these two co-circulating strains. These findings mechanistically link immune history, variant neutralization, antibody repertoire and variant infection risk, and suggest that vaccination regimens in children should prioritize neutralization breadth.
T. Johnston, Rahul Subramanian, Wakinyan Benhamou et al.· bioRxiv· 0 citations
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