ICAM-5/Telencephalin Is a Functional Entry Receptor for Enterovirus D68

Cell Host Microbe. 2016 Nov 9;20(5):631-641. doi: 10.1016/j.chom.2016.09.013. Epub 2016 Oct 27.


Enterovirus D68 (EV-D68) is a member of the Picornaviridae family. Although EV-D68-associated infection was once considered rare, it has been increasing in recent years. EV-D68 infection is most frequently associated with respiratory illness. However, it has also been implicated in a polio-like neurological disorder, acute flaccid myelitis. Although sialic acid has been implicated in EV-D68 entry, the existence of a protein receptor has yet to be clarified. Here we identify neuron-specific intercellular adhesion molecule 5 (ICAM-5/telencephalin) as a cellular receptor for sialic acid-dependent and -independent EV-D68 viruses. EV-D68 bound specifically and efficiently to ICAM-5, and replication of EV-D68 in diverse cell types was inhibited by soluble ICAM-5 fragments. ICAM-5 silencing attenuated EV-D68 replication in permissive cells, and ICAM-5 expression in non-permissive cells allowed EV-D68 replication. The discovery of a neuron-specific adhesion molecule as an EV-D68 receptor has important implications for EV-D68 pathogenesis and may facilitate the development of novel intervention strategies.

Keywords: EV-D68; ICAM-5/telencephalin; acute flaccid myelitis; enterovirus; entry receptor; picornaviridae; respiratory illness.

MeSH terms

  • Cell Adhesion Molecules / metabolism*
  • Enterovirus D, Human / physiology*
  • Humans
  • Nerve Tissue Proteins / metabolism*
  • Protein Binding
  • Receptors, Virus / metabolism*
  • Sialic Acids / metabolism
  • Virus Attachment
  • Virus Internalization*


  • Cell Adhesion Molecules
  • ICAM5 protein, human
  • Nerve Tissue Proteins
  • Receptors, Virus
  • Sialic Acids