scholarly journals Modelling West Nile Virus and Usutu Virus Pathogenicity in Human Neural Stem Cells

Viruses ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 882 ◽  
Author(s):  
Silvia Riccetti ◽  
Alessandro Sinigaglia ◽  
Giovanna Desole ◽  
Norbert Nowotny ◽  
Marta Trevisan ◽  
...  
Keyword(s):  
Stem Cells ◽  
West Nile Virus ◽  
Neural Stem Cells ◽  
Clinical Manifestations ◽  
Fetal Brain ◽  
Adult Brain ◽  
Interferon Response ◽  
Type I ◽  
West Nile ◽  
Usutu Virus

West Nile virus (WNV) and Usutu virus (USUV) are genetically related neurotropic mosquito-borne flaviviruses, which frequently co-circulate in nature. Despite USUV seeming to be less pathogenic for humans than WNV, the clinical manifestations induced by these two viruses often overlap and may evolve to produce severe neurological complications. The aim of this study was to investigate the effects of WNV and USUV infection on human induced pluripotent stem cell-derived neural stem cells (hNSCs), as a model of the neural progenitor cells in the developing fetal brain and in adult brain. Zika virus (ZIKV), a flavivirus with known tropism for NSCs, was used as the positive control. Infection of hNSCs and viral production, effects on cell viability, apoptosis, and innate antiviral responses were compared among viruses. WNV displayed the highest replication efficiency and cytopathic effects in hNSCs, followed by USUV and then ZIKV. In these cells, both WNV and USUV induced the overexpression of innate antiviral response genes at significantly higher levels than ZIKV. Expression of interferon type I, interleukin-1β and caspase-3 was significantly more elevated in WNV- than USUV-infected hNSCs, in agreement with the higher neuropathogenicity of WNV and the ability to inhibit the interferon response pathway.

scholarly journals The Naturally Attenuated Kunjin Strain of West Nile Virus Shows Enhanced Sensitivity to the Host Type I Interferon Response

2011 ◽  
Vol 85 (11) ◽  
pp. 5664-5668 ◽  
Author(s):  
S. Daffis ◽  
H. M. Lazear ◽  
W. J. Liu ◽  
M. Audsley ◽  
M. Engle ◽  
...  
Keyword(s):  
West Nile Virus ◽  
Type I Interferon ◽  
Interferon Response ◽  
Type I ◽  
West Nile ◽  
Enhanced Sensitivity ◽  
Host Type

scholarly journals Interferon Regulatory Factor IRF-7 Induces the Antiviral Alpha Interferon Response and Protects against Lethal West Nile Virus Infection

2008 ◽  
Vol 82 (17) ◽  
pp. 8465-8475 ◽  
Author(s):  
Stephane Daffis ◽  
Melanie A. Samuel ◽  
Mehul S. Suthar ◽  
Brian C. Keller ◽  
Michael Gale ◽  
...  
Keyword(s):  
West Nile Virus ◽  
Cortical Neurons ◽  
Interferon Regulatory Factor ◽  
Interferon Response ◽  
Type I ◽  
Type I Ifn ◽  
Regulatory Factor ◽  
West Nile

ABSTRACT Type I interferon (IFN-α/β) comprises a family of immunomodulatory cytokines that are critical for controlling viral infections. In cell culture, many RNA viruses trigger IFN responses through the binding of RNA recognition molecules (RIG-I, MDA5, and TLR-3) and induction of interferon regulatory factor IRF-3-dependent gene transcription. Recent studies with West Nile virus (WNV) have shown that type I IFN is essential for restricting infection and that a deficiency of IRF-3 results in enhanced lethality. However, IRF-3 was not required for optimal systemic IFN production in vivo or in vitro in macrophages. To begin to define the transcriptional factors that regulate type I IFN after WNV infection, we evaluated IFN induction and virus control in IRF-7−/− mice. Compared to congenic wild-type mice, IRF-7−/− mice showed increased lethality after WNV infection and developed early and elevated WNV burdens in both peripheral and central nervous system tissues. As a correlate, a deficiency of IRF-7 blunted the systemic type I IFN response in mice. Consistent with this, IFN-α gene expression and protein production were reduced and viral titers were increased in IRF-7−/− primary macrophages, fibroblasts, dendritic cells, and cortical neurons. In contrast, in these cells the IFN-β response remained largely intact. Our data suggest that the early protective IFN-α response against WNV occurs through an IRF-7-dependent transcriptional signal.

scholarly journals West Nile Virus and Usutu Virus Co-Circulation in Europe: Epidemiology and Implications

2019 ◽  
Vol 7 (7) ◽  
pp. 184 ◽  
Author(s):  
Zannoli ◽  
Sambri
Keyword(s):  
West Nile Virus ◽  
Human Health ◽  
Clinical Manifestations ◽  
Geographic Range ◽  
Vector Species ◽  
West Nile ◽  
Usutu Virus ◽  
Human Infections

West Nile virus (WNV) and Usutu virus (USUV) are neurotropic mosquito-borne flaviviruses that may infect humans. Although WNV is much more widespread and plays a much larger role in human health, the two viruses are characterized by similar envelope antigens, clinical manifestations, and present overlapping in terms of geographic range of transmission, host, and vector species. This review highlights some of the most relevant aspects of WNV and USUV human infections in Europe, and the possible implications of their co-circulation.

scholarly journals Functional maturation of human neural stem cells in a 3D bioengineered brain model enriched with fetal brain-derived matrix

2019 ◽  
Author(s):  
Disha Sood ◽  
Dana M. Cairns ◽  
Jayanth M. Dabbi ◽  
Charu Ramakrishnan ◽  
Karl Deisseroth ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Brain Tissue ◽  
Fetal Brain ◽  
Functional Differentiation ◽  
Adult Brain ◽  
Human Neural Stem Cells ◽  
Functional Maturation ◽  
Enriched Cultures

AbstractBrain extracellular matrix (ECM) is often overlooked in vitro brain tissue models, despite its instructive roles during development. Using developmental stage-sourced brain ECM in reproducible 3D bioengineered culture systems, we demonstrate enhanced functional differentiation of human induced neural stem cells (hiNSCs) into healthy neurons and astrocytes. Particularly, fetal brain tissue-derived ECM supported long-term maintenance of differentiated neurons, demonstrated by morphology, gene expression and secretome profiling. Astrocytes were evident within the second month of differentiation, and reactive astrogliosis was inhibited in brain ECM-enriched cultures when compared to unsupplemented cultures. Functional maturation of the differentiated hiNSCs within fetal ECM-enriched cultures was confirmed by calcium signaling and unsupervised cluster analysis. Additionally, the study identified native biochemical cues in decellularized ECM with notable comparisons between fetal and adult brain-derived ECMs. The development of novel brain-specific biomaterials for generating mature in vitro brain models provides an important path forward for interrogation of neuron-glia interactions.

scholarly journals Functional maturation of human neural stem cells in a 3D bioengineered brain model enriched with fetal brain-derived matrix

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Disha Sood ◽  
Dana M. Cairns ◽  
Jayanth M. Dabbi ◽  
Charu Ramakrishnan ◽  
Karl Deisseroth ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Brain Tissue ◽  
Fetal Brain ◽  
Functional Differentiation ◽  
Adult Brain ◽  
Human Neural Stem Cells ◽  
Functional Maturation ◽  
Enriched Cultures

AbstractBrain extracellular matrix (ECM) is often overlooked in vitro brain tissue models, despite its instructive roles during development. Using developmental stage-sourced brain ECM in reproducible 3D bioengineered culture systems, we demonstrate enhanced functional differentiation of human induced neural stem cells (hiNSCs) into healthy neurons and astrocytes. Particularly, fetal brain tissue-derived ECM supported long-term maintenance of differentiated neurons, demonstrated by morphology, gene expression and secretome profiling. Astrocytes were evident within the second month of differentiation, and reactive astrogliosis was inhibited in brain ECM-enriched cultures when compared to unsupplemented cultures. Functional maturation of the differentiated hiNSCs within fetal ECM-enriched cultures was confirmed by calcium signaling and spectral/cluster analysis. Additionally, the study identified native biochemical cues in decellularized ECM with notable comparisons between fetal and adult brain-derived ECMs. The development of novel brain-specific biomaterials for generating mature in vitro brain models provides an important path forward for interrogation of neuron-glia interactions.

scholarly journals Co‐Infections: Simultaneous Detections of West Nile Virus and Usutu Virus in Birds from Germany

2021 ◽  
Author(s):  
Pauline Dianne Santos ◽  
Friederike Michel ◽  
Claudia Wylezich ◽  
Dirk Höper ◽  
Markus Keller ◽  
...  
Keyword(s):  
West Nile Virus ◽  
West Nile ◽  
Usutu Virus

scholarly journals Screening of Mosquitoes for West Nile Virus and Usutu Virus in Croatia, 2015–2020

2021 ◽  
Vol 6 (2) ◽  
pp. 45
Author(s):  
Ana Klobucar ◽  
Vladimir Savic ◽  
Marcela Curman Posavec ◽  
Suncica Petrinic ◽  
Urska Kuhar ◽  
...  
Keyword(s):  
West Nile Virus ◽  
Culex Pipiens ◽  
Rt Pcr ◽  
West Nile ◽  
Usutu Virus ◽  
Culex Pipiens Complex ◽  
Mammalian Origin ◽  
Mosquito Pool ◽  
The City ◽  
Generation Sequencing

In the period from 2015 to 2020, an entomological survey for the presence of West Nile virus (WNV) and Usutu virus (USUV) in mosquitoes was performed in northwestern Croatia. A total of 20,363 mosquitoes were sampled in the City of Zagreb and Međimurje county, grouped in 899 pools and tested by real-time RT-PCR for WNV and USUV RNA. All pools were negative for WNV while one pool each from 2016 (Aedes albopictus), 2017 (Culex pipiens complex), 2018 (Cx. pipiens complex), and 2019 (Cx. pipiens complex), respectively, was positive for USUV. The 2018 and 2019 positive pools shared 99.31% nucleotide homology within the USUV NS5 gene and both clustered within USUV Europe 2 lineage. The next-generation sequencing of one mosquito pool (Cx. pipiens complex) collected in 2018 in Zagreb confirmed the presence of USUV and revealed several dsDNA and ssRNA viruses of insect, bacterial and mammalian origin.

scholarly journals Neural stem cells: involvement in adult neurogenesis and CNS repair

2008 ◽  
Vol 363 (1500) ◽  
pp. 2111-2122 ◽  
Author(s):  
Hideyuki Okano ◽  
Kazunobu Sawamoto
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Cell Transplantation ◽  
Adult Neurogenesis ◽  
Embryonic Stem ◽  
Adult Brain ◽  
Therapeutic Interventions ◽  
Cell Transplantation Therapy ◽  
Transplantation Therapy

Recent advances in stem cell research, including the selective expansion of neural stem cells (NSCs) in vitro , the induction of particular neural cells from embryonic stem cells in vitro , the identification of NSCs or NSC-like cells in the adult brain and the detection of neurogenesis in the adult brain (adult neurogenesis), have laid the groundwork for the development of novel therapies aimed at inducing regeneration in the damaged central nervous system (CNS). There are two major strategies for inducing regeneration in the damaged CNS: (i) activation of the endogenous regenerative capacity and (ii) cell transplantation therapy. In this review, we summarize the recent findings from our group and others on NSCs, with respect to their role in insult-induced neurogenesis (activation of adult NSCs, proliferation of transit-amplifying cells, migration of neuroblasts and survival and maturation of the newborn neurons), and implications for therapeutic interventions, together with tactics for using cell transplantation therapy to treat the damaged CNS.

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