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

TY - JOUR

T1 - Enterovirus 71 infection of human airway organoids reveals VP1-145 as a viral infectivity determinant

AU - van der Sanden, Sabine M G

AU - Sachs, Norman

AU - Koekkoek, Sylvie M

AU - Koen, Gerrit

AU - Pajkrt, Dasja

AU - Clevers, Hans

AU - Wolthers, Katja C

PY - 2018/5/9

Y1 - 2018/5/9

N2 - 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.

AB - 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.

KW - Amino Acid Motifs

KW - Amino Acid Sequence

KW - Capsid Proteins/chemistry

KW - Enterovirus A, Human/chemistry

KW - Enterovirus Infections/virology

KW - Humans

KW - Kinetics

KW - Organoids/virology

KW - Sequence Alignment

KW - Virulence

KW - Virus Replication

U2 - 10.1038/s41426-018-0077-2

DO - 10.1038/s41426-018-0077-2

M3 - Article

C2 - 29743570

SN - 2222-1751

VL - 7

SP - 84

JO - Emerging Microbes & Infections

JF - Emerging Microbes & Infections

IS - 1

ER -