Shao Qiang, Herrlinger Stephanie, Zhu Ya-Nan, Yang Mei, Goodfellow Forrest, Stice Steven L, Qi Xiao-Peng, Brindley Melinda A, Chen Jian-Fu
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA.
Department of Genetics, Department of Biochemistry & Molecular Biology, University of Georgia, Athens, GA 30602, USA.
Development. 2017 Nov 15;144(22):4114-4124. doi: 10.1242/dev.156752. Epub 2017 Oct 9.
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.
寨卡病毒（ZIKV）有亚洲和非洲两个谱系，尚未对它们对发育中大脑的影响进行比较。登革病毒（DENV）是寨卡病毒的近亲，与寨卡病毒共同传播。在此，我们用登革病毒2（DENV2）对胚胎小鼠脑进行脑内接种，发现DENV2足以因神经祖细胞（NPC）和神经元中细胞死亡增加而导致脑尺寸变小。与目前正在传播的寨卡病毒亚洲谱系（MEX1-44）相比，DENV2生长较慢，导致的神经元死亡较少，且不会导致出生后动物死亡。令人惊讶的是，我们的并列比较发现，非洲寨卡病毒分离株（MR-766）在导致脑损伤和出生后致死方面比MEX1-44更具效力。与MEX1-44相比，MR-766在NPC和发育中的大脑中生长更快，在NPC和神经元中导致更明显的细胞死亡，从而导致更严重的神经元损失。总之，这些结果表明DENV2足以导致脑尺寸变小，并表明寨卡病毒非洲谱系比亚洲谱系毒性更强，导致的脑损伤更严重。
