Scientists suggest that doublecortin is modulated following infection of the brain by ZIKV
A Zika virus (ZIKV) outbreak has been ongoing in central and south America for the past 2 years, and has raised global concerns with regards to public health. ZIKV has been shown to infect neural progenitor cells (NPCs) and inhibits cell proliferation, growth of neurospheres and brain organoids, suggesting that the neuropathology induced by ZIKV might be associated with NPC cell fate. However, the molecular mechanism(s) of ZIKV affecting neurogenesis still remains to be elucidated.
In a recent study, the research group led by Prof. LUO Minhua in Wuhan Institute of Virology of the Chinese Academy of Sciences utilized the primary human fetal NPC and the microinjection of fetal mouse brain to study the mechanisms of how ZIKV infection causes fetal brain development disorders.
The scientists found that NPCs were vulnerable to ZIKV infection, that multiple signaling pathways and cellular functions associated with neurogenesis were impaired by the infection, and that ZIKV infection downregulates DCX expression in NPC and mouse fetal brain, which further related to the decreased thickness of cortex layers. Further screening indicated that ZIKV NS4A and NS5 were related to the downregulation of doublecortin (DCX) in NPCs, which may contribute to the cortical structure defects caused by ZIKV.
In summary, their data extend the understanding of these two viral proteins in affecting cell fate of human NPCs. Further studies will be required to elucidate the specific means by which ZIKV NS4A, and NS5 influence the expression level of DCX.
The results have been published in Frontiers in Microbiology entitled "Proteomic Analysis of Zika Virus Infected Primary Human Fetal Neural Progenitors Suggests a Role for Doublecortin in the Pathological Consequences of Infection in the Cortex".
The study was supported by the National Key Research and Development Program of China and the Major Program of Guangzhou healthcare collaborative innovation foundation, the Sino-Africa joint research center, Chinese Academy of Sciences and the National Nature Science Foundation of China.
ZIKV infection decreases the expression of DCX in mouse fetal brain and causes defects in cortical layer structure. Image by LUO Minhua