Disrupted neuronal expression of autism risk genes and white matter micro-organization after infant Zika infection

Venkata-Viswanadh Edara; Sienna Freeman; Maureen Sampson; Kathryn M. Moore; Rebecca Richardson; Nils Schoof; Divine Burgess; Michelle J. Lee; Gregory K. Tharp; Roza Vlasova; Shane Taylor; Ariana Hodjatzadeh; Yihana P. Melendez-Alejandro; Samia M. Abdallah; Esther W. Ndungu; Ava K. Mascarenhas; Chao-Hsiung Hsu; Tsang-Wei Tu; Martin Styner; Mehul S. Suthar; Mar M. Sanchez; Steven E. Bosinger; Mark W. Burke; Steven A. Sloan; Jessica Raper; Ann Chahroudi

doi:10.1172/jci.insight.203088

¹Department of Pediatrics, Emory University School of Medicine, Atlanta, United States of America

²Emory National Primate Research Center, Atlanta, United States of America

³Department of Human Genetics, Emory University School of Medicine, Atlanta, United States of America

⁴Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Department of Physiology and Biophysics, Howard University, Washington DC, United States of America

⁶Molecular Imaging Laboratory, Department of Radiology, Howard University, Washington DC, United States of America

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¹Department of Pediatrics, Emory University School of Medicine, Atlanta, United States of America

²Emory National Primate Research Center, Atlanta, United States of America

³Department of Human Genetics, Emory University School of Medicine, Atlanta, United States of America

⁴Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Department of Physiology and Biophysics, Howard University, Washington DC, United States of America

⁶Molecular Imaging Laboratory, Department of Radiology, Howard University, Washington DC, United States of America

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¹Department of Pediatrics, Emory University School of Medicine, Atlanta, United States of America

²Emory National Primate Research Center, Atlanta, United States of America

³Department of Human Genetics, Emory University School of Medicine, Atlanta, United States of America

⁴Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Department of Physiology and Biophysics, Howard University, Washington DC, United States of America

⁶Molecular Imaging Laboratory, Department of Radiology, Howard University, Washington DC, United States of America

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¹Department of Pediatrics, Emory University School of Medicine, Atlanta, United States of America

²Emory National Primate Research Center, Atlanta, United States of America

³Department of Human Genetics, Emory University School of Medicine, Atlanta, United States of America

⁴Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Department of Physiology and Biophysics, Howard University, Washington DC, United States of America

⁶Molecular Imaging Laboratory, Department of Radiology, Howard University, Washington DC, United States of America

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¹Department of Pediatrics, Emory University School of Medicine, Atlanta, United States of America

²Emory National Primate Research Center, Atlanta, United States of America

³Department of Human Genetics, Emory University School of Medicine, Atlanta, United States of America

⁴Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Department of Physiology and Biophysics, Howard University, Washington DC, United States of America

⁶Molecular Imaging Laboratory, Department of Radiology, Howard University, Washington DC, United States of America

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¹Department of Pediatrics, Emory University School of Medicine, Atlanta, United States of America

²Emory National Primate Research Center, Atlanta, United States of America

³Department of Human Genetics, Emory University School of Medicine, Atlanta, United States of America

⁴Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Department of Physiology and Biophysics, Howard University, Washington DC, United States of America

⁶Molecular Imaging Laboratory, Department of Radiology, Howard University, Washington DC, United States of America

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¹Department of Pediatrics, Emory University School of Medicine, Atlanta, United States of America

²Emory National Primate Research Center, Atlanta, United States of America

³Department of Human Genetics, Emory University School of Medicine, Atlanta, United States of America

⁴Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Department of Physiology and Biophysics, Howard University, Washington DC, United States of America

⁶Molecular Imaging Laboratory, Department of Radiology, Howard University, Washington DC, United States of America

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¹Department of Pediatrics, Emory University School of Medicine, Atlanta, United States of America

²Emory National Primate Research Center, Atlanta, United States of America

³Department of Human Genetics, Emory University School of Medicine, Atlanta, United States of America

⁴Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Department of Physiology and Biophysics, Howard University, Washington DC, United States of America

⁶Molecular Imaging Laboratory, Department of Radiology, Howard University, Washington DC, United States of America

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¹Department of Pediatrics, Emory University School of Medicine, Atlanta, United States of America

²Emory National Primate Research Center, Atlanta, United States of America

³Department of Human Genetics, Emory University School of Medicine, Atlanta, United States of America

⁴Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Department of Physiology and Biophysics, Howard University, Washington DC, United States of America

⁶Molecular Imaging Laboratory, Department of Radiology, Howard University, Washington DC, United States of America

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¹Department of Pediatrics, Emory University School of Medicine, Atlanta, United States of America

²Emory National Primate Research Center, Atlanta, United States of America

³Department of Human Genetics, Emory University School of Medicine, Atlanta, United States of America

⁴Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Department of Physiology and Biophysics, Howard University, Washington DC, United States of America

⁶Molecular Imaging Laboratory, Department of Radiology, Howard University, Washington DC, United States of America

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¹Department of Pediatrics, Emory University School of Medicine, Atlanta, United States of America

²Emory National Primate Research Center, Atlanta, United States of America

³Department of Human Genetics, Emory University School of Medicine, Atlanta, United States of America

⁴Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Department of Physiology and Biophysics, Howard University, Washington DC, United States of America

⁶Molecular Imaging Laboratory, Department of Radiology, Howard University, Washington DC, United States of America

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¹Department of Pediatrics, Emory University School of Medicine, Atlanta, United States of America

²Emory National Primate Research Center, Atlanta, United States of America

³Department of Human Genetics, Emory University School of Medicine, Atlanta, United States of America

⁴Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Department of Physiology and Biophysics, Howard University, Washington DC, United States of America

⁶Molecular Imaging Laboratory, Department of Radiology, Howard University, Washington DC, United States of America

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¹Department of Pediatrics, Emory University School of Medicine, Atlanta, United States of America

²Emory National Primate Research Center, Atlanta, United States of America

³Department of Human Genetics, Emory University School of Medicine, Atlanta, United States of America

⁴Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Department of Physiology and Biophysics, Howard University, Washington DC, United States of America

⁶Molecular Imaging Laboratory, Department of Radiology, Howard University, Washington DC, United States of America

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¹Department of Pediatrics, Emory University School of Medicine, Atlanta, United States of America

²Emory National Primate Research Center, Atlanta, United States of America

³Department of Human Genetics, Emory University School of Medicine, Atlanta, United States of America

⁴Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Department of Physiology and Biophysics, Howard University, Washington DC, United States of America

⁶Molecular Imaging Laboratory, Department of Radiology, Howard University, Washington DC, United States of America

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¹Department of Pediatrics, Emory University School of Medicine, Atlanta, United States of America

²Emory National Primate Research Center, Atlanta, United States of America

³Department of Human Genetics, Emory University School of Medicine, Atlanta, United States of America

⁴Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Department of Physiology and Biophysics, Howard University, Washington DC, United States of America

⁶Molecular Imaging Laboratory, Department of Radiology, Howard University, Washington DC, United States of America

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¹Department of Pediatrics, Emory University School of Medicine, Atlanta, United States of America

²Emory National Primate Research Center, Atlanta, United States of America

³Department of Human Genetics, Emory University School of Medicine, Atlanta, United States of America

⁴Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Department of Physiology and Biophysics, Howard University, Washington DC, United States of America

⁶Molecular Imaging Laboratory, Department of Radiology, Howard University, Washington DC, United States of America

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¹Department of Pediatrics, Emory University School of Medicine, Atlanta, United States of America

²Emory National Primate Research Center, Atlanta, United States of America

³Department of Human Genetics, Emory University School of Medicine, Atlanta, United States of America

⁴Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Department of Physiology and Biophysics, Howard University, Washington DC, United States of America

⁶Molecular Imaging Laboratory, Department of Radiology, Howard University, Washington DC, United States of America

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¹Department of Pediatrics, Emory University School of Medicine, Atlanta, United States of America

²Emory National Primate Research Center, Atlanta, United States of America

³Department of Human Genetics, Emory University School of Medicine, Atlanta, United States of America

⁴Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Department of Physiology and Biophysics, Howard University, Washington DC, United States of America

⁶Molecular Imaging Laboratory, Department of Radiology, Howard University, Washington DC, United States of America

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¹Department of Pediatrics, Emory University School of Medicine, Atlanta, United States of America

²Emory National Primate Research Center, Atlanta, United States of America

³Department of Human Genetics, Emory University School of Medicine, Atlanta, United States of America

⁴Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Department of Physiology and Biophysics, Howard University, Washington DC, United States of America

⁶Molecular Imaging Laboratory, Department of Radiology, Howard University, Washington DC, United States of America

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¹Department of Pediatrics, Emory University School of Medicine, Atlanta, United States of America

²Emory National Primate Research Center, Atlanta, United States of America

³Department of Human Genetics, Emory University School of Medicine, Atlanta, United States of America

⁴Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Department of Physiology and Biophysics, Howard University, Washington DC, United States of America

⁶Molecular Imaging Laboratory, Department of Radiology, Howard University, Washington DC, United States of America

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¹Department of Pediatrics, Emory University School of Medicine, Atlanta, United States of America

²Emory National Primate Research Center, Atlanta, United States of America

³Department of Human Genetics, Emory University School of Medicine, Atlanta, United States of America

⁴Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Department of Physiology and Biophysics, Howard University, Washington DC, United States of America

⁶Molecular Imaging Laboratory, Department of Radiology, Howard University, Washington DC, United States of America

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¹Department of Pediatrics, Emory University School of Medicine, Atlanta, United States of America

²Emory National Primate Research Center, Atlanta, United States of America

³Department of Human Genetics, Emory University School of Medicine, Atlanta, United States of America

⁴Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Department of Physiology and Biophysics, Howard University, Washington DC, United States of America

⁶Molecular Imaging Laboratory, Department of Radiology, Howard University, Washington DC, United States of America

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¹Department of Pediatrics, Emory University School of Medicine, Atlanta, United States of America

²Emory National Primate Research Center, Atlanta, United States of America

³Department of Human Genetics, Emory University School of Medicine, Atlanta, United States of America

⁴Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Department of Physiology and Biophysics, Howard University, Washington DC, United States of America

⁶Molecular Imaging Laboratory, Department of Radiology, Howard University, Washington DC, United States of America

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¹Department of Pediatrics, Emory University School of Medicine, Atlanta, United States of America

²Emory National Primate Research Center, Atlanta, United States of America

³Department of Human Genetics, Emory University School of Medicine, Atlanta, United States of America

⁴Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Department of Physiology and Biophysics, Howard University, Washington DC, United States of America

⁶Molecular Imaging Laboratory, Department of Radiology, Howard University, Washington DC, United States of America

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¹Department of Pediatrics, Emory University School of Medicine, Atlanta, United States of America

²Emory National Primate Research Center, Atlanta, United States of America

³Department of Human Genetics, Emory University School of Medicine, Atlanta, United States of America

⁴Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Department of Physiology and Biophysics, Howard University, Washington DC, United States of America

⁶Molecular Imaging Laboratory, Department of Radiology, Howard University, Washington DC, United States of America

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¹Department of Pediatrics, Emory University School of Medicine, Atlanta, United States of America

²Emory National Primate Research Center, Atlanta, United States of America

³Department of Human Genetics, Emory University School of Medicine, Atlanta, United States of America

⁴Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Department of Physiology and Biophysics, Howard University, Washington DC, United States of America

⁶Molecular Imaging Laboratory, Department of Radiology, Howard University, Washington DC, United States of America

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JCI Insight. https://doi.org/10.1172/jci.insight.203088.
Copyright © 2026, Edara et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Published September 24, 2026 - Version history

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.

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Disrupted neuronal expression of autism risk genes and white matter micro-organization after infant Zika infection

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Disrupted neuronal expression of autism risk genes and white matter micro-organization after infant Zika infection

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