Mechanisms of disrupted neurodevelopment after Zika virus infection in infancy

  1. Venkata-Viswanadh Edara
  2. Sienna Freeman
  3. Maureen Sampson
  4. Kathryn Moore
  5. Rebecca Richardson
  6. Nils Schoof
  7. Divine Burgess
  8. Michelle J. Lee
  9. Gregory Tharp
  10. Roza Vlasova
  11. Shane Taylor
  12. Ariana Hodjatzadeh
  13. Yihana Melendez-Alejandro
  14. Samia Abdallah
  15. Esther Ndungu
  16. Ava Mascarenhas
  17. Chao-Hsiung Hsu
  18. Tsang-Wei Tu
  19. Martin Styner
  20. Mehul S. Suthar
  21. Mar M. Sanchez
  22. Steven Bosinger
  23. Mark Burke
  24. Steven A. Sloan
  25. Jessica Raper
  26. Ann Chahroudi

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Abstract

Congenital and early-life Zika virus (ZIKV) infection can result in neurologic deficits. Precise mechanisms of injury, especially in the more subtle presentation of postnatal infection, are not fully elucidated. Here, we defined the effects of ZIKV on the developing brain using single cell transcriptomics, histopathology and design-based stereology, diffusion MRI, and neurobehavioral assessments in infant rhesus macaques. ZIKV upregulated interferon-stimulated genes in activated microglia and cell death pathways in neurons and downregulated metabolism and differentiation genes in mature oligodendrocytes. Abnormal micro-organization of the corpus collosum and limbic white matter tracts was seen on diffusion weighted imaging. A curated gene set associated with autism spectrum disorder risk was negatively enriched in inhibitory and excitatory neurons from ZIKV-infected infants, with increased emotional reactivity already evident two weeks following infection. From single cells to organism-level behaviors, these results define the pathways and processes disrupted by early-life ZIKV infection.

Article activity feed

  1. Rapid Reviews Infectious Diseases

    Jean Pierre Schatzmann Peron, Julys da Fonseca Palmeira, Raquel das Neves Almeida

    Review 2: "Mechanisms of Disrupted Neurodevelopment After Zika Virus Infection in Infancy"

    Reviewers considered the study relevant and comprehensive, emphasizing the value of the non-human primate model and the integration of datasets, but also noted several limitations.

  2. Rapid Reviews Infectious Diseases

    Jaclyn Schwarz

    Review 1: "Mechanisms of Disrupted Neurodevelopment After Zika Virus Infection in Infancy"

    Reviewers considered the study relevant and comprehensive, emphasizing the value of the non-human primate model and the integration of datasets, but also noted several limitations.

  4. Version published to 10.64898/2026.01.26.701807 on bioRxiv