Abstract
Prenatal Zika virus (ZIKV) exposure can result in outcomes ranging from severe birth defects to subtle developmental delays, yet the underlying mechanisms remain unclear. Using a translational rhesus macaque model, we assess visual, auditory, and neurodevelopmental outcomes through 12 months of age following first-trimester ZIKV inoculation. Pregnant macaques, either flavivirus-naive or with prior dengue virus (DENV) exposure, are inoculated with Asian or African ZIKV lineages. Maternal viremia duration, placental viral burden, and neutralizing antibody titers vary but are not associated with developmental outcomes. At 12 months, ZIKV-exposed infants exhibit altered maternal attachment behaviors and reduced inhibition toward novel sensory stimuli. Visual evoked potentials are impaired at 3 months but normalize by 12 months; hearing loss is more frequent but not statistically significant. These outcomes are driven by ZIKV exposure itself, independent of maternal infection characteristics. Our findings highlight the limitations of maternal biomarkers in risk prediction and support incorporating infant-focused developmental outcomes in studies of maternal interventions.
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Acknowledgements
We thank the Wisconsin National Primate Research Center, specifically Behavioral Management Services, Scientific Protocol Implementation Services, Pathology Services, and Veterinary Services for their assistance with this project. We thank David O’Connor for insightful discussions on experimental design. This project was supported in part by NIH P01AI132132. We used ChatGPT 4o to assist with improving readability. We thank Saswati Bhattacharya, Taylor Treadway, and Nikunj Makwana for their contributions. This work was supported by the National Institutes of Health grants R01 AI153130 (to K.K.A. and E.L.M.), P01AI132132 (David O’Connor), and P30EY016665 (Vision Research Core), and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development grant P50HD105353 (Waisman Center).
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Conceptualization: K.K.A. and E.L.M. Methodology: K.K.A., A.H., A.M.W., C.R., M.N., H.A.S., J.V.H., T.C.F., M.T.A., and E.L.M. Investigation: K.K.A., B.B., E.R.R., J.K., N.P.K., A.M.M., S.W., V.M., J.R.D., S.K., F.E., R.V.S., A. Shah, A. Sun, J.G., A.K., C.K., A.H., A.M.W., C.R., M.N., P.B., H.A.S., J.V.H., M.T.A., and E.L.M. Visualization: E.R.R., A. Shah, A. Sun, J.V.H., and E.L.M. Funding acquisition: K.K.A. and E.L.M. Project administration: K.K.A. and E.L.M. Supervision: K.K.A., A.H., M.N., H.A.S., S.C., and T.C.F. Writing—original draft: K.K.A., B.B., E.R.R., and J.K. Writing—review & editing: K.K.A., B.B., E.R.R., J.K., N.P.K., A.M.M., S.W., V.M., J.R.D., S.K., F.E., R.V.S., A. Shah, A. Sun, J.G., A.K., C.K., A.H., A.M.W., C.R., M.N., P.B., S.C., H.A.S., J.V.H., M.T.A., T.C.F., and E.L.M.
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J.V.H. is a consultant for a company called OSOD, A Merit Company, which provides consulting services to the pharmaceutical industry. The remaining authors declare no competing interests.
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Ausderau, K.K., Boerigter, B., Razo, E.R. et al. Prenatal Zika virus exposure disrupts social-emotional development and cortical visual function in infant macaques. Nat Commun (2026). https://doi.org/10.1038/s41467-026-68517-x
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DOI: https://doi.org/10.1038/s41467-026-68517-x
