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Parechovirus infection in human brain organoids: host innate inflammatory response and not neuro-infectivity correlates to neurologic disease

ABSTRACT: 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.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain

SUBMITTER: Akos Vegvari

LAB HEAD: Akos Vegvari

PROVIDER: PXD047238 | Pride | 2024-02-14

REPOSITORIES: Pride

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