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Development. 2017 Nov 15;144(22):4114-4124. doi: 10.1242/dev.156752. Epub 2017 Oct 9.

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

Author information

1
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA.
2
Department of Genetics, Department of Biochemistry & Molecular Biology, University of Georgia, Athens, GA 30602, USA.
3
Regenerative Bioscience Center, University of Georgia, Athens, GA 30602, USA.
4
Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.
5
Department of Infectious Diseases, Department of Population Health and Center for Vaccines and Immunology, University of Georgia, Athens, GA 30602, USA.
6
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA Jianfu@usc.edu.

Abstract

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 with 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 the African ZIKV isolate (MR-766) is more potent at causing brain damage and postnatal lethality than MEX1-44. In comparison with 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 toxic and causes more potent brain damage than the Asian lineage.

KEYWORDS:

African ZIKV (MR-766); Asian ZIKV; Brain damage; DENV2; Neuronal death

PMID:
28993398
PMCID:
PMC5719247
DOI:
10.1242/dev.156752
[Indexed for MEDLINE]
Free PMC Article

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