Molecular signatures associated with ZIKV exposure in human cortical neural progenitors

Zhang, Feiran; Hammack, Christy; Ogden, Sarah; Cheng, Yichen; Lee, Emily M.; Wen, Zhexing; Qian, Xuyu; Nguyen, Ha Nam; Li, Yujing; Yao, Bing; Xu, Miao; Xu, Tianlei; Chen, Li; Wang, Zhiqin; Feng, Hao; Huang, Wei; Yoon, Ki‐Jun; Shan, Chao; Huang, Luoxiu; Qin, Zhaohui; Christian, Kimberly M.; Shi, Pei Yong; Xu, Mingjiang; Xia, Menghang; Zheng, Wei; Wu, Hao; Song, Hongjun; Tang, Hengli; Guo, Ming; Jin, Peng

doi:10.1093/nar/gkw765

Cited by 155 publications

(138 citation statements)

References 52 publications

(60 reference statements)

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“…The same study went further to show that at the molecular level the infection resulted in downregulation of cell-cycle genes and upregulation of apoptosis genes in NPCs. This was further evidenced by abnormal progression of cell cycle, increased cell death/apoptosis, and disrupted neurogenesis by the same study as well as many others 167–173 . For a more in-depth overview of the subject see review by Ming et al 174 .…”

Section: Induced-pluripotent Stem Cell Models Of Neurodevelopmentasupporting

confidence: 70%

Human induced pluripotent stem cells for modelling neurodevelopmental disorders

et al. 2017

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Currently, we have a poor understanding of the pathogenesis of neurodevelopmental disorders, owing to the fact that post-mortem and imaging studies are only capable of measuring the postnatal status quo and offer little insight into the processes that give rise to the observed outcomes. Human induced pluripotent stem cells (hiPSCs) in principle should prove powerful in elucidating the pathways that give rise to neurodevelopmental disorders. HiPSCs are embryonic stem cell-like cells that can be derived from somatic cells. They retain the unique genetic signature of the individual from whom they were derived from, and thus allow researchers to recapitulate that individual’s idiosyncratic neural development in a dish. In the case of diseased individuals, we can reenact the disease-altered trajectory of brain development and examine how and why phenotypic and molecular abnormalities arise in these diseased brains. In this paper, we review various aspects of hiPSC biology and experimental design as well as discuss existing hiPSC models of neurodevelopmental disorders. As already shown by some studies discussed in this review, our hope is that iPSCs will illuminate the pathophysiology of developmental disorders of the CNS and lead to therapeutic avenues for the millions that today suffer from neurodevelopmental disorders.

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Section: Induced-pluripotent Stem Cell Models Of Neurodevelopmentasupporting

confidence: 70%

Human induced pluripotent stem cells for modelling neurodevelopmental disorders

et al. 2017

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“…Some of the genes differentially regulated by ZIKV had been previously found by the transcriptome analysis of infected human neural progenitors41516. Upregulation of CDKN1A gene (cyclin-dependent kinase inhibitor 1A) is related to cell cycle arrest by preventing the phosphorylation of cyclin-dependent kinases.…”

Section: Discussionmentioning

confidence: 99%

Zika virus disrupts molecular fingerprinting of human neurospheres

Garcez

Nascimento

Vasconcelos

et al. 2017

Sci Rep

107

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Zika virus (ZIKV) has been associated with microcephaly and other brain abnormalities; however, the molecular consequences of ZIKV to human brain development are still not fully understood. Here we describe alterations in human neurospheres derived from induced pluripotent stem (iPS) cells infected with the strain of Zika virus that is circulating in Brazil. Combining proteomics and mRNA transcriptional profiling, over 500 proteins and genes associated with the Brazilian ZIKV infection were found to be differentially expressed. These genes and proteins provide an interactome map, which indicates that ZIKV controls the expression of RNA processing bodies, miRNA biogenesis and splicing factors required for self-replication. It also suggests that impairments in the molecular pathways underpinning cell cycle and neuronal differentiation are caused by ZIKV. These results point to biological mechanisms implicated in brain malformations, which are important to further the understanding of ZIKV infection and can be exploited as therapeutic potential targets to mitigate it.

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“…Recent reports have also shown inhibition of ECM pathways by both DENV and ZIKV (Afroz et al, 2016; Zhang et al, 2016), suggesting a common pathophysiologic pathway for these flaviviruses. ECM proteins are widely expressed in the developing and adult nervous system and may also be critical for lymphocyte trafficking (Barros et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Zika Virus Persistence in the Central Nervous System and Lymph Nodes of Rhesus Monkeys

Aïd

Abbink

Larocca

et al. 2017

Cell

191

194

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SUMMARY Zika virus (ZIKV) is associated with severe neuropathology in neonates as well as Guillain-Barre syndrome and other neurologic disorders in adults. Prolonged viral shedding has been reported in semen, suggesting the presence of anatomic viral reservoirs. Here we show that ZIKV can persist in cerebrospinal fluid (CSF) and lymph nodes (LN) of infected rhesus monkeys for weeks after virus has been cleared from peripheral blood, urine, and mucosal secretions. ZIKV-specific neutralizing antibodies correlated with rapid clearance of virus in peripheral blood but remained undetectable in CSF for the duration of the study. Viral persistence in both CSF and LN correlated with upregulation of mechanistic target of rapamycin (mTOR), proinflammatory, and anti-apoptotic signaling pathways, as well as downregulation of extracellular matrix and cell signaling pathways. These data raise the possibility that persistent or occult neurologic and lymphoid disease may occur following clearance of peripheral virus in ZIKV-infected individuals.

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Molecular signatures associated with ZIKV exposure in human cortical neural progenitors

Cited by 155 publications

References 52 publications

Human induced pluripotent stem cells for modelling neurodevelopmental disorders

Human induced pluripotent stem cells for modelling neurodevelopmental disorders

Zika virus disrupts molecular fingerprinting of human neurospheres

Zika Virus Persistence in the Central Nervous System and Lymph Nodes of Rhesus Monkeys

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