Parechovirus infection in human brain organoids: host innate inflammatory response and not neuro-infectivity correlates to neurologic disease
Summary
Picornaviruses are a leading cause of central nervous system (CNS) infections. While genotypes such as parechovirus A3 (PeV-A3) and echovirus 11 (E11) can elicit severe neurological disease, the highly prevalent PeV-A1 is not associated with CNS disease. Here, we expand our current understanding of these differences in PeV-A CNS disease using human brain organoids and clinical isolates of the two PeV-A genotypes. Our data indicate that PeV-A1 and A3 specific differences in neurological disease are not due to infectivity of CNS cells as both viruses productively infect brain organoids with a similar cell tropism. Proteomic analysis shows that PeV-A infection significantly alters the host cell metabolism. The inflammatory response following PeV-A3 (and E11 infection) is significantly more potent than that upon PeV-A1 infection. Collectively, our findings align with clinical observations and suggest a role for neuroinflammation, rather than viral replication, in PeV-A3 (and E11) infection. © 2024. The Author(s).
| Authors | Capendale PE, García-Rodríguez I, Ambikan AT, Mulder LA, Depla JA, Freeze E, Koen G, Calitz C, Sood V, Vieira de Sá R, Neogi U, Pajkrt D, Sridhar A, Wolthers KC |
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| Journal | Nature communications |
| Publication Date | 2024 Mar 21;15(1):2532 |
| PubMed | 38514653 |
| PubMed Central | PMC10958052 |
| DOI | 10.1038/s41467-024-46634-9 |