Erratum: ZIKA virus elicits P53 activation and genotoxic stress in human neural progenitors similar to mutations involved in severe forms of genetic microcephaly and p53

Ghouzzi, Vincent El; Bianchi, F.; Molineris, Ivan; Mounce, Bryan C.; Berto, Gaia; Rak, Malgorzata; Lebon, Sophie; Aubry, Laëtitia; Tocco, Chiara; Gai, Marta; Chiotto, Alessandra MA; Solinas, Francesco; Pallavicini, Gianmarco; Simon‐Lorière, Etienne; Passemard, Sandrine; Vignuzzi, Marco; Gressèns, Pierre; Cunto, Ferdinando Di

doi:10.1038/cddis.2016.446

Cited by 16 publications

(8 citation statements)

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“…Moreover, ZIKV-BR infection led to G2/M arrest in μBS when compared to ZIKV-UG and DENV-1 (Figure 4B). Similar results have demonstrated that ZIKV-BR infection deregulates the cell cycle, resulting in attenuated hNPC growth (Dang et al, 2016; Garcez et al, 2016; Tang et al, 2016; Ghouzzi et al, 2017). Furthermore, phagocytosis of apoptotic cells by microglia cells has been described as a general mechanism to clear these cells from tissues (Arandjelovic and Ravichandran, 2015).…”

Section: Discussionsupporting

confidence: 80%

Microglia Increase Inflammatory Responses in iPSC-Derived Human BrainSpheres

et al. 2018

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Human induced pluripotent stem cells (iPSCs), together with 21st century cell culture methods, have the potential to better model human physiology with applications in toxicology, disease modeling, and the study of host-pathogen interactions. Several models of the human brain have been developed recently, demonstrating cell-cell interactions of multiple cell types with physiologically relevant 3D structures. Most current models, however, lack the ability to represent the inflammatory response in the brain because they do not include a microglial cell population. Microglia, the resident immunocompetent phagocytes in the central nervous system (CNS), are not only important in the inflammatory response and pathogenesis; they also function in normal brain development, strengthen neuronal connections through synaptic pruning, and are involved in oligodendrocyte and neuronal survival. Here, we have successfully introduced a population of human microglia into 3D human iPSC-derived brain spheres (BrainSpheres, BS) through co-culturing cells of the Immortalized Human Microglia – SV40 cell line with the BS model (μBS). We detected an inflammatory response to lipopolysaccharides (LPS) and flavivirus infection, which was only elicited in the model when microglial cells were present. A concentration of 20 ng/mL of LPS increased gene expression of the inflammatory cytokines interleukin-6 (IL-6), IL-10, and IL-1β, with maximum expression at 6–12 h post-exposure. Increased expression of the IL-6, IL-1β, tumor necrosis factor alpha (TNF-α), and chemokine (C-C motif) ligand 2 (CCL2) genes was observed in μBS following infection with Zika and Dengue Virus, suggesting a stronger inflammatory response in the model when microglia were present than when only astrocyte, oligodendrocyte, and neuronal populations were represented. Microglia innately develop within cerebral organoids (Nature communications)1, our findings suggest that the μBS model is more physiologically relevant and has potential applications in infectious disease and host-pathogen interactions research.

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Section: Discussionsupporting

confidence: 80%

Microglia Increase Inflammatory Responses in iPSC-Derived Human BrainSpheres

et al. 2018

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“…Further, a variety of apoptosis markers were detected in neural parenchyma isolated from clinical cases, including FASL, FAS, Bax, and caspase-3 ( de Sousa et al, 2018 ). And numerous reports show that neural cell apoptosis increases after ZIKV infection ( Huang W.-C. et al, 2016 ; Li et al, 2016 ; Qian et al, 2016 ; Souza et al, 2016 ; Ghouzzi et al, 2017 ). For example, ZIKV preferentially induces apoptosis of neuro progenitor cells (NPCs), which is confirmed by the activation of caspases-3/7, -8, and -9 and the significantly elevated gene expression of TRAIL, as well as ultrastructural and flow cytometry analysis ( Tang et al, 2016 ; Jungmann et al, 2017 ; Lee et al, 2020 ).…”

Section: Apoptosis During Flavivirus-infectionmentioning

confidence: 99%

The Dual Regulation of Apoptosis by Flavivirus

et al. 2021

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Apoptosis is a form of programmed cell death, which maintains cellular homeostasis by eliminating pathogen-infected cells. It contains three signaling pathways: death receptor pathway, mitochondria-mediated pathway, and endoplasmic reticulum pathway. Its importance in host defenses is highlighted by the observation that many viruses evade, hinder or destroy apoptosis, thereby weakening the host’s immune response. Flaviviruses such as Dengue virus, Japanese encephalitis virus, and West Nile virus utilize various strategies to activate or inhibit cell apoptosis. This article reviews the research progress of apoptosis mechanism during flaviviruses infection, including flaviviruses proteins and subgenomic flaviviral RNA to regulate apoptosis by interacting with host proteins, as well as various signaling pathways involved in flaviviruses-induced apoptosis, which provides a scientific basis for understanding the pathogenesis of flaviviruses and helps in developing an effective antiviral therapy.

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“…ZIKV infection triggers apoptosis of human neural progenitor cells (134), as evidenced by the activation of caspase 3, 7, 8 and 9, leading to cortical thinning and microcephaly (98). Inhibition of tumor suppressor protein p53 prevents ZIKV-mediated apoptosis of neural progenitor cells, confirming p53 is involved in ZIKVinduced apoptosis (135). The ZIKV-C induces ribosomal stress and apoptosis, and the C protein of DENV has the same function (136).…”

Section: Apoptosismentioning

confidence: 97%

Flaviviruses: Innate Immunity, Inflammasome Activation, Inflammatory Cell Death, and Cytokines

et al. 2022

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The innate immune system is the host’s first line of defense against the invasion of pathogens including flavivirus. The programmed cell death controlled by genes plays an irreplaceable role in resisting pathogen invasion and preventing pathogen infection. However, the inflammatory cell death, which can trigger the overflow of a large number of pro-inflammatory cytokines and cell contents, will initiate a severe inflammatory response. In this review, we summarized the current understanding of the innate immune response, inflammatory cell death pathway and cytokine secretion regulation during Dengue virus, West Nile virus, Zika virus, Japanese encephalitis virus and other flavivirus infections. We also discussed the impact of these flavivirus and viral proteins on these biological processes. This not only provides a scientific basis for elucidating the pathogenesis of flavivirus, but also lays the foundation for the development of effective antiviral therapies.

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Erratum: ZIKA virus elicits P53 activation and genotoxic stress in human neural progenitors similar to mutations involved in severe forms of genetic microcephaly and p53

Cited by 16 publications

References 0 publications

Microglia Increase Inflammatory Responses in iPSC-Derived Human BrainSpheres

Microglia Increase Inflammatory Responses in iPSC-Derived Human BrainSpheres

The Dual Regulation of Apoptosis by Flavivirus

Flaviviruses: Innate Immunity, Inflammasome Activation, Inflammatory Cell Death, and Cytokines

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