Parechovirus Infection in Human Brain Organoids: Host Innate Inflammatory Response and not Neuro-infectivity Correlates to Neurologic Disease

Picornaviruses, including parechovirus A3 (PeV-A3) and echovirus 11 (E11), can cause severe central nervous system (CNS) infections, while the prevalent PeV-A1 genotype is not associated with CNS disease. To understand these differences, researchers utilized human brain organoids and clinical isolates of PeV-A genotypes. They found that both PeV-A1 and A3 infect brain organoids similarly, indicating that differences in neurological disease are not due to infectivity of CNS cells. However, proteomic analysis revealed that PeV-A infection alters host cell metabolism, and the inflammatory response to PeV-A3 (and E11) is more potent than PeV-A1 infection. These findings suggest that neuroinflammation, rather than viral replication, plays a significant role in PeV-A3 (and E11) infection, aligning with clinical observations.