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

Author

Listed:
  • Pamela E. Capendale

    (University of Amsterdam
    University of Amsterdam)

  • Inés García-Rodríguez

    (University of Amsterdam
    University of Amsterdam)

  • Anoop T. Ambikan

    (Campus Flemingsberg)

  • Lance A. Mulder

    (University of Amsterdam
    University of Amsterdam)

  • Josse A. Depla

    (University of Amsterdam
    Department of Research & Development)

  • Eline Freeze

    (University of Amsterdam
    University of Amsterdam)

  • Gerrit Koen

    (University of Amsterdam)

  • Carlemi Calitz

    (University of Amsterdam
    University of Amsterdam)

  • Vikas Sood

    (Campus Flemingsberg
    Jamia Hamdard)

  • Renata Vieira de Sá

    (University of Amsterdam
    Campus Flemingsberg)

  • Ujjwal Neogi

    (Campus Flemingsberg)

  • Dasja Pajkrt

    (University of Amsterdam
    University of Amsterdam)

  • Adithya Sridhar

    (University of Amsterdam
    University of Amsterdam
    Amsterdam UMC)

  • Katja C. Wolthers

    (University of Amsterdam)

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 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.

Suggested Citation

  • Pamela E. Capendale & Inés García-Rodríguez & Anoop T. Ambikan & Lance A. Mulder & Josse A. Depla & Eline Freeze & Gerrit Koen & Carlemi Calitz & Vikas Sood & Renata Vieira de Sá & Ujjwal Neogi & Dasj, 2024. "Parechovirus infection in human brain organoids: host innate inflammatory response and not neuro-infectivity correlates to neurologic disease," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46634-9
    DOI: 10.1038/s41467-024-46634-9
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    References listed on IDEAS

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    1. Madeline A. Lancaster & Magdalena Renner & Carol-Anne Martin & Daniel Wenzel & Louise S. Bicknell & Matthew E. Hurles & Tessa Homfray & Josef M. Penninger & Andrew P. Jackson & Juergen A. Knoblich, 2013. "Cerebral organoids model human brain development and microcephaly," Nature, Nature, vol. 501(7467), pages 373-379, September.
    2. Kanako Watanabe & Tomoichiro Oka & Hirotaka Takagi & Sergei Anisimov & Shun-ichi Yamashita & Yoshinori Katsuragi & Masahiko Takahashi & Masaya Higuchi & Tomotake Kanki & Akihiko Saitoh & Masahiro Fuji, 2023. "Myeloid-associated differentiation marker is an essential host factor for human parechovirus PeV-A3 entry," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    3. Fernanda R. Cugola & Isabella R. Fernandes & Fabiele B. Russo & Beatriz C. Freitas & João L. M. Dias & Katia P. Guimarães & Cecília Benazzato & Nathalia Almeida & Graciela C. Pignatari & Sarah Romero , 2016. "The Brazilian Zika virus strain causes birth defects in experimental models," Nature, Nature, vol. 534(7606), pages 267-271, June.
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