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Enterovirus D68 receptor usage: from static attachment to dynamic entry.

Dongxue Liu1,2, Zhilin Ji3, Xiangyu Zheng4,5

  • 1Institute of Virology and AIDS Research, The First Hospital of Jilin University, Changchun, Jilin, China.

Journal of Virology
|December 30, 2025
PubMed
Summary
This summary is machine-generated.

Enterovirus D68 (EV-D68) uses multiple receptors, including sialic acid, ICAM-5, and MFSD6, to infect cells. This receptor plasticity explains its spread in respiratory and nervous systems, guiding new therapeutic development.

Keywords:
ICAM-5MFSD6acute flaccid myelitisenterovirus D68sialic acidviral entryviral receptor

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Area of Science:

  • Virology
  • Molecular Biology
  • Immunology

Background:

  • Enterovirus D68 (EV-D68) is a reemerging pathogen causing severe respiratory illness and acute flaccid myelitis (AFM).
  • Viral entry mechanisms are key to understanding EV-D68 tropism and pathogenesis.
  • Previous models focused on sialic acid, but recent discoveries reveal a more complex receptor landscape.

Purpose of the Study:

  • To review the evolving understanding of EV-D68 receptor usage.
  • To synthesize current knowledge on viral attachment factors and entry receptors.
  • To explore the implications of receptor versatility for viral evolution and therapeutic strategies.

Main Methods:

  • Literature review of studies on EV-D68 receptor interactions.
  • Analysis of established and newly identified viral receptors.
  • Discussion of the functional significance of receptor usage in different cell types.

Main Results:

  • Sialic acid acts as an attachment factor and uncoating trigger for older EV-D68 strains.
  • ICAM-5 is a neuron-specific receptor explaining neurotropism in AFM.
  • MFSD6 is identified as a crucial entry receptor for diverse EV-D68 strains in respiratory and neuronal cells.

Conclusions:

  • EV-D68 exhibits remarkable receptor plasticity, utilizing sialic acid, ICAM-5, and MFSD6.
  • This adaptability influences tissue tropism, viral evolution, and disease manifestation.
  • Understanding receptor-virus interactions, especially the MFSD6 interface, is crucial for developing novel EV-D68 therapeutics.