Enterovirus 71 infection of human airway organoids reveals VP1-145 as a viral infectivity determinant

Sabine M G van der Sanden, Norman Sachs, Sylvie M Koekkoek, Gerrit Koen, Dasja Pajkrt, Hans Clevers, Katja C Wolthers

Research output: Contribution to journal/periodicalArticleScientificpeer-review

Abstract

Human enteroviruses frequently cause severe diseases in children. Human enteroviruses are transmitted via the fecal-oral route and respiratory droplets, and primary replication occurs in the gastro-intestinal and respiratory tracts; however, how enteroviruses infect these sites is largely unknown. Human intestinal organoids have recently proven to be valuable tools for studying enterovirus-host interactions in the intestinal tract. In this study, we demonstrated the susceptibility of a newly developed human airway organoid model for enterovirus 71 (EV71) infection. We showed for the first time in a human physiological model that EV71 replication kinetics are strain-dependent. A glutamine at position 145 of the VP1 capsid protein was identified as a key determinant of infectivity, and residues VP1-98K and VP1-104D were identified as potential infectivity markers. The results from this study provide new insights into EV71 infectivity in the human airway epithelia and demonstrate the value of organoid technology for virus research.

Original languageEnglish
Pages (from-to)84
JournalEmerging Microbes & Infections
Volume7
Issue number1
DOIs
Publication statusPublished - 09 May 2018

Keywords

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Capsid Proteins/chemistry
  • Enterovirus A, Human/chemistry
  • Enterovirus Infections/virology
  • Humans
  • Kinetics
  • Organoids/virology
  • Sequence Alignment
  • Virulence
  • Virus Replication

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