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

Wei Wei, Haoran Guo, Junliang Chang, Yingzi Yu, Guanchen Liu, Nannan Zhang, Stephen H. Willard, Shu Zheng, Xiao Fang Yu

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)631-641
Number of pages11
JournalCell Host and Microbe
Issue number5
StatePublished - Nov 9 2016


  • EV-D68
  • ICAM-5/telencephalin
  • acute flaccid myelitis
  • enterovirus
  • entry receptor
  • picornaviridae
  • respiratory illness

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology


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