ICAM-1 functions as a functional receptor for encephalomyocarditis virus and reveals a compensatory interplay with ICAM-4.

ICAM-1 functions as a key receptor for EMCV entry, with high-affinity binding to viral proteins VP1 and VP2, and is essential for infection in human and mouse cells.

• Why it matters: Understanding EMCV entry mechanisms is crucial because it is a widespread zoonotic pathogen causing piglet death, and its receptors are currently unknown, limiting antiviral development.
• What they did: The study identified ICAM-1 as a receptor by demonstrating its direct binding to EMCV proteins and showing that blocking ICAM-1 impairs infection; additionally, ICAM-4 acts as a receptor in ICAM-1-deficient models.
• The result: Targeting ICAM-1 domain 1 may offer a potential antiviral strategy against EMCV, as both ICAM-1 and ICAM-4 are involved in viral entry.