Sialic acid-dependent cell entry of human enterovirus D68

Nat Commun. 2015 Nov 13;6:8865. doi: 10.1038/ncomms9865.


Human enterovirus D68 (EV-D68) is a causative agent of childhood respiratory diseases and has now emerged as a global public health threat. Nevertheless, knowledge of the tissue tropism and pathogenesis of EV-D68 has been hindered by a lack of studies on the receptor-mediated EV-D68 entry into host cells. Here we demonstrate that cell surface sialic acid is essential for EV-D68 to bind to and infect susceptible cells. Crystal structures of EV-D68 in complex with sialylated glycan receptor analogues show that they bind into the 'canyon' on the virus surface. The sialic acid receptor induces a cascade of conformational changes in the virus to eject a fatty-acid-like molecule that regulates the stability of the virus. Thus, virus binding to a sialic acid receptor and to immunoglobulin-like receptors used by most other enteroviruses share a conserved mechanism for priming viral uncoating and facilitating cell entry.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Enterovirus D, Human / genetics
  • Enterovirus D, Human / physiology*
  • Enterovirus Infections / virology*
  • Humans
  • N-Acetylneuraminic Acid / metabolism*
  • Receptors, Cell Surface / metabolism
  • Receptors, Virus / metabolism
  • Virus Internalization*


  • Receptors, Cell Surface
  • Receptors, Virus
  • sialic acid receptor
  • N-Acetylneuraminic Acid