Key result
PeV-A3 and E11 infection in human brain organoids induced a significantly more potent inflammatory response compared to PeV-A1, despite similar cell tropism and infectivity.
Why the study?
Picornaviruses are a leading cause of CNS infections, but why genotypes like PeV-A3 and E11 cause severe neurological disease while prevalent PeV-A1 does not remains poorly understood.
The severe neurological disease associated with PeV-A3 compared to PeV-A1 is likely driven by a potent inflammatory response rather than differences in viral neuro-infectivity or cell tropism.
Answers are grounded in this paper and cite their sources.
Organoid models link stronger inflammation to PeV-A3/E11 neurovirulence; hypothesis-generating for mechanisms and therapies in neonatal CNS infections.
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 PeV-A genotypes. Our data indicates 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 showed that PeV-A infection significantly alters the host cell metabolism. The inflammatory response following PeV-A3 (and E11 infection) was significantly more potent than that upon PeV-A1 infection. Collectively, our findings align with clinical observations and suggest a role for inflammatory-mediated neurology, rather than viral replication, in PeV-A3 (and E11) infection.
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Capendale et al. (2023) studied Parechovirus A central nervous system infection. Parechovirus A3 and Echovirus 11 vs. Parechovirus A1 and MOCK was evaluated on Host innate inflammatory response and viral replication. PeV-A3 and E11 infection in human brain organoids induced a significantly more potent inflammatory response compared to PeV-A1, despite similar cell tropism and infectivity.
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