Aminopeptidase N is a receptor for hedgehog merbecoviruses

Min Jin1, Victoria A Jefferson2, Zhe Zhao3

  • 1Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.

Insights

Hedgehog merbecoviruses use Aminopeptidase N (APN) to enter host cells. This discovery clarifies viral entry mechanisms and informs zoonotic risk assessments for these MERS-CoV relatives.

Area of Science:

  • Virology
  • Structural Biology
  • Zoonosis Research

Background:

  • Merbecoviruses, related to MERS-CoV, are found in hedgehogs globally.
  • Concerns exist regarding zoonotic transmission potential to humans and animals.
  • The host cell entry mechanism for hedgehog merbecoviruses was previously unknown.

Purpose of the Study:

  • To identify the host cell entry receptor for hedgehog merbecoviruses.
  • To understand the molecular basis of species barriers for merbecovirus entry.
  • To inform risk assessments for potential viral emergence and zoonotic transmission.

Main Methods:

  • Tested European hedgehog (Erinaceus europaeus) coronavirus receptor orthologues.
  • Utilized single-cycle pseudotype and replication-competent virus assays.
  • Performed protein binding assays and cryo-electron microscopy (cryo-EM).

Main Results:

  • Identified Aminopeptidase N (APN) as the entry receptor for hedgehog merbecoviruses.
  • Confirmed APN as the receptor using multiple experimental approaches.
  • Cryo-EM revealed a unique viral glycoprotein-APN interaction interface, distinct from other betacoronaviruses.

Conclusions:

  • Aminopeptidase N is a key receptor for hedgehog merbecovirus entry.
  • The unique binding interface explains species-specific entry barriers.
  • Findings expand knowledge of betacoronavirus receptors and zoonotic potential.

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