Replication of early and recent Zika virus isolates throughout mouse brain development
Amy B Rosenfeld1, David J Doobin2, Audrey L Warren3
1Department of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, NY 10032; abr22@cumc.columbia.edu.
Summary
Zika virus (ZIKV) infection in fetuses causes congenital Zika virus syndrome (cZVS) by disrupting brain development. Uninfected cell death and impaired neuronal migration are key factors in ZIKV neuropathology.
Area of Science:
- Neuroscience
- Virology
- Developmental Biology
Background:
- Fetal Zika virus (ZIKV) infection causes congenital Zika virus syndrome (cZVS), characterized by cortical malformations and microcephaly.
- The specific impacts of ZIKV on cortical development remain largely unknown.
Purpose of the Study:
- To investigate the effects of ZIKV infection on developing brain tissue and understand its contribution to cZVS.
- To identify sites of ZIKV replication and characterize neuropathological changes in the developing brain.
Main Methods:
- Organotypic brain slice cultures from embryonic mice of various gestational ages were used.
- ZIKV replication sites and neuropathological alterations were analyzed.
- Apoptosis in infected and surrounding cells was assessed.
Main Results:
- ZIKV replicated in the neocortical proliferative zone, radial columns, and developing midbrain.
- Infected radial units were surrounded by apoptotic uninfected cells, suggesting programmed cell death limits viral spread.
- Neocortical cytoarchitecture was altered, including disrupted radial glial progenitor cells and impaired neuronal migration.
- All tested ZIKV isolates demonstrated neurotropism.
Conclusions:
- ZIKV infection significantly interferes with multiple critical aspects of neurodevelopment.
- The death of uninfected cells is a critical factor in ZIKV-induced neuropathology.
- ZIKV's disruption of neurodevelopment contributes to the complex features of congenital Zika virus syndrome.
