Parechovirus A Infection of the Intestinal Epithelium: Differences Between Genotypes A1 and A3

• Published in: Frontiers in cellular and infection microbiology Vol. 11; p. 740662
• Main Authors: García-Rodríguez, Inés, van Eijk, Hetty, Koen, Gerrit, Pajkrt, Dasja, Sridhar, Adithya, Wolthers, Katja C
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 01-11-2021
• Subjects: Cellular and Infection Microbiology; Child, Preschool; enteroids; Feces; Genotype; human organoids; Humans; Intestinal Mucosa; parechovirus; Parechovirus - genetics; PeV-A; Picornaviridae Infections; polarized epithelium; Transwell; polarized epithelium; PeV-A; parechovirus; enteroids; Transwell; human organoids
• ISSN: 2235-2988; 2235-2988
• DOI: 10.3389/fcimb.2021.740662

Human parechovirus (PeV-A), one of the species within the
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
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.