About this item:

211 Views | 188 Downloads

Author Notes:

To whom correspondence should be addressed: Ann Chahroudi, achahro@emory.edu.

A.C. designed the study with input from M.M., M.A., M.S.S., J.W., D.H.O., T.H.V., R.P.J., D.I.W. and G.S.

M.S.S. provided the virus.

J.R. and M.C.A. performed the HI test and interpreted the data.

Z.K-B., M.M.S, and X.Z. interpreted the neuroimaging.

D.F., E.F., E.E., and M.S. provided tools for imaging analysis.

S.G. and M.W.B. performed histopathology.

S.K.B. and J.W. performed and analyzed ELISA and neutralization assays.

J.T.O., C.E.M., M.S.S., V.K.B, D.M.M., and D.I.W. performed and analyzed data from virologic assays with help from C.M.

J.H., C.M., and M.M. processed samples.

S.M.J. and J.K.C. provided animal care and collected samples.

A.C., M.M., and V.A. wrote the manuscript with help from the other authors.

We thank S. Ehnert and the YNPRC Division of Research Resources for expert assistance with animal procedures, M. Thompson and the Emory Environmental Health and Safety Office for supervising environmental infection control in the YNPRC nursery, and A. McElroy for training and helpful discussions.

We would like to acknowledge Kristina De Paris from the University of North Carolina and Koen Van Rompay from the California National Primate Research Center (CNPRC) for providing control infant brains for histopathology (Grant numbers R01 DE022287 and R01 DE019064 to K.D.P. and P51 OD011107 to CNPRC).

D.H.O. is a paid a member of the Institutional Biosafety Committee for Takeda Vaccines, that is involved in ZIKV research.

Subjects:

Research Funding:

This work was supported by the Pilot Grant Program of the YNPRC (P51 OD011132), the Emory Center for Childhood Infections and Vaccines, and Children’s Healthcare of Atlanta. Research reported in this publication was supported by the National Library of Medicine of the National Institutes of Health under Award Number T15LM007088 (to E. F.).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Cell Biology
  • Medicine, Research & Experimental
  • Research & Experimental Medicine
  • NEONATAL HIPPOCAMPAL-LESIONS
  • CENTRAL-NERVOUS-SYSTEM
  • ADULT SOCIAL-BEHAVIOR
  • RHESUS-MONKEYS
  • RECOGNITION MEMORY
  • MACACA-MULATTA
  • NEUROIMAGING FINDINGS
  • PREFRONTAL CORTEX
  • PICTORIAL ESSAY
  • ACUTE STRESSOR

Postnatal Zika virus infection is associated with persistent abnormalities in brain structure, function, and behavior in infant macaques

Show all authors Show less authors

Tools:

Journal Title:

Science Translational Medicine

Volume:

Volume 10, Number 435

Publisher:

, Pages eaao6975-eaao6975

Type of Work:

Article | Post-print: After Peer Review

Abstract:

No claim to original U.S. Government Works The Zika virus (ZIKV) epidemic is associated with fetal brain lesions and other serious birth defects classified as congenital ZIKV syndrome. Postnatal ZIKV infection in infants and children has been reported; however, data on brain anatomy, function, and behavioral outcomes following infection are absent. We show that postnatal ZIKV infection of infant rhesus macaques (RMs) results in persistent structural and functional alterations of the central nervous system compared to age-matched controls. We demonstrate ZIKV lymphoid tropism and neurotropism in infant RMs and histopathologic abnormalities in the peripheral and central nervous systems including inflammatory infiltrates, astrogliosis, and Wallerian degeneration. Structural and resting-state functional magnetic resonance imaging (MRI/rs-fMRI) show persistent enlargement of lateral ventricles, maturational changes in specific brain regions, and altered functional connectivity (FC) between brain areas involved in emotional behavior and arousal functions, including weakened amygdala-hippocampal connectivity in two of two ZIKV-infected infant RMs several months after clearance of ZIKV RNA from peripheral blood. ZIKV infection also results in distinct alterations in the species-typical emotional reactivity to acute stress, which were predicted by the weak amygdala-hippocampal FC. We demonstrate that postnatal ZIKV infection of infants in this model affects neurodevelopment, suggesting that long-term clinical monitoring of pediatric cases is warranted.

Copyright information:

© 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science.

Export to EndNote