The African Zika virus MR-766 is more virulent and causes more severe brain damage than current Asian lineage and Dengue virus

• DOI: 10.1242/dev.156752
• Publication Date: 2017-10-10T00:10:32Z
• Authors: Qiang Shao; Stephanie Herrlinger; Ya-Nan Zhu; Mei Yang; Forrest Goodfellow; Steven L. Stice; Xiao-Peng Qi; Melinda A. Brindley; Jian-Fu Chen
• Keywords: Cerebral Cortex; Neurons; 0303 health sciences; Asia; Cell Death; Virulence; Brain; Zika Virus; Dengue Virus; 3. Good health; Mice, Inbred C57BL; 03 medical and health sciences; Animals, Newborn; Neural Stem Cells; Africa; Microcephaly; Animals; Gliosis; Microglia; Phylogeny

The Zika virus (ZIKV) has two lineages, Asian and African, and their impact on developing brains has not been compared. Dengue virus (DENV) is a close family member of ZIKV and co-circulates with ZIKV. Here we performed intracerebral inoculation of embryonic mouse brains with dengue virus 2 (DENV2), and found that DENV2 is sufficient to cause smaller brain size due to increased cell death in neural progenitor cells (NPCs) and neurons. Compared to the currently circulating Asian lineage of ZIKV (MEX1-44), DENV2 grows slower, causes less neuronal death, and fails to cause postnatal animal death. Surprisingly, our side-by-side comparison uncovered that African ZIKV isolate (MR-766) is more potent in causing brain damage and postnatal lethality than MEX1-44. In comparison to MEX1-44, MR-766 grows faster in NPCs and in the developing brain, and causes more pronounced cell death in NPCs and neurons, resulting in more severe neuronal loss. Together, these results reveal that DENV2 is sufficient to cause smaller brain sizes, and suggest that the ZIKV African lineage is more virulent and causes more severe brain damage than the Asian lineage.