TY - JOUR
T1 - Parechovirus A Infection of the Intestinal Epithelium
T2 - Differences Between Genotypes A1 and A3
AU - García-Rodríguez, Inés
AU - van Eijk, Hetty
AU - Koen, Gerrit
AU - Pajkrt, Dasja
AU - Sridhar, Adithya
AU - Wolthers, Katja C.
N1 - Funding Information: This research was co-funded by the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Sklowdowska-Curie Grant Agreement OrganoVIR (grant 812673) and the PPP Allowance (Focus-on-Virus) made available by Health Holland, Top Sector Life Sciences & Publisher Copyright: Copyright © 2021 García-Rodríguez, van Eijk, Koen, Pajkrt, Sridhar and Wolthers.
PY - 2021/11/1
Y1 - 2021/11/1
N2 - Human parechovirus (PeV-A), one of the species within the Picornaviridae family, is known to cause disease in humans. The most commonly detected genotypes are PeV-A1, associated with mild gastrointestinal disease in young children, and PeV-A3, linked to severe disease with neurological symptoms in neonates. As PeV-A are detectable in stool and nasopharyngeal samples, entry is speculated to occur via the respiratory and gastro-intestinal routes. In this study, we characterized PeV-A1 and PeV-A3 replication and tropism in the intestinal epithelium using a primary 2D model based on human fetal enteroids. This model was permissive to infection with lab-adapted strains and clinical isolates of PeV-A1, but for PeV-A3, infection could only be established with clinical isolates. Replication was highest with infection established from the basolateral side with apical shedding for both genotypes. Compared to PeV-A1, replication kinetics of PeV-A3 were slower. Interestingly, there was a difference in cell tropism with PeV-A1 infecting both Paneth cells and enterocytes, while PeV-A3 infected mainly goblet cells. This difference in cell tropism may explain the difference in replication kinetics and associated disease in humans.
AB - Human parechovirus (PeV-A), one of the species within the Picornaviridae family, is known to cause disease in humans. The most commonly detected genotypes are PeV-A1, associated with mild gastrointestinal disease in young children, and PeV-A3, linked to severe disease with neurological symptoms in neonates. As PeV-A are detectable in stool and nasopharyngeal samples, entry is speculated to occur via the respiratory and gastro-intestinal routes. In this study, we characterized PeV-A1 and PeV-A3 replication and tropism in the intestinal epithelium using a primary 2D model based on human fetal enteroids. This model was permissive to infection with lab-adapted strains and clinical isolates of PeV-A1, but for PeV-A3, infection could only be established with clinical isolates. Replication was highest with infection established from the basolateral side with apical shedding for both genotypes. Compared to PeV-A1, replication kinetics of PeV-A3 were slower. Interestingly, there was a difference in cell tropism with PeV-A1 infecting both Paneth cells and enterocytes, while PeV-A3 infected mainly goblet cells. This difference in cell tropism may explain the difference in replication kinetics and associated disease in humans.
KW - PeV-A
KW - Transwell
KW - enteroids
KW - human organoids
KW - parechovirus
KW - polarized epithelium
UR - http://www.scopus.com/inward/record.url?scp=85119112537&partnerID=8YFLogxK
U2 - https://doi.org/10.3389/fcimb.2021.740662
DO - https://doi.org/10.3389/fcimb.2021.740662
M3 - Article
C2 - 34790587
SN - 2235-2988
VL - 11
JO - Frontiers in cellular and infection microbiology
JF - Frontiers in cellular and infection microbiology
M1 - 740662
ER -