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

Area of Science:

• Virology
• Gastroenterology
• Human Infectious Diseases

Background:

• Human parechovirus (PeV-A) belongs to the Picornaviridae family and causes human illness.
• PeV-A1 is linked to mild gastrointestinal issues in children, while PeV-A3 is associated with severe neurological disease in neonates.
• Respiratory and gastrointestinal routes are suspected entry pathways for PeV-A.

Purpose of the Study:

• To characterize the replication and cell tropism of PeV-A1 and PeV-A3 in the intestinal epithelium.
• To utilize a primary 2D human fetal enteroid model for studying PeV-A infection dynamics.

Main Methods:

• Infection of human fetal enteroids with PeV-A1 and PeV-A3 clinical isolates and lab-adapted strains.
• Assessment of viral replication kinetics and cell tropism within the enteroid model.
• Analysis of viral shedding from basolateral to apical surfaces.

Main Results:

• The enteroid model supported PeV-A1 infection with both lab-adapted and clinical strains, but PeV-A3 only with clinical isolates.
• Both genotypes exhibited highest replication with basolateral infection and apical shedding.
• PeV-A3 demonstrated slower replication kinetics compared to PeV-A1.
• PeV-A1 infected Paneth cells and enterocytes, whereas PeV-A3 primarily infected goblet cells.

Conclusions:

• Distinct cell tropism and replication kinetics were observed between PeV-A1 and PeV-A3 in a human intestinal model.
• The differential cell tropism of PeV-A genotypes may underlie the varying disease manifestations in humans.
• Human fetal enteroids provide a valuable model for studying PeV-A pathogenesis.