scholarly journals Advances in Zika Virus–Host Cell Interaction: Current Knowledge and Future Perspectives

2019 ◽  
Vol 20 (5) ◽  
pp. 1101 ◽  
Author(s):  
Jae Lee ◽  
Ok Shin
Keyword(s):  
Host Cell ◽  
Zika Virus ◽  
Current Knowledge ◽  
Cell Interaction ◽  
Human Pathogens ◽  
Zikv Infection ◽  
In Vivo Models ◽  
Host Cell Interaction

Emerging mosquito-transmitted RNA viruses, such as Zika virus (ZIKV) and Chikungunya represent human pathogens of an immense global health problem. In particular, ZIKV has emerged explosively since 2007 to cause a series of epidemics in the South Pacific and most recently in the Americas. Although typical ZIKV infections are asymptomatic, ZIKV infection during pregnancy is increasingly associated with microcephaly and other fetal developmental abnormalities. In the last few years, genomic and molecular investigations have established a remarkable progress on the pathogenic mechanisms of ZIKV infection using in vitro and in vivo models. Here, we highlight recent advances in ZIKV-host cell interaction studies, including cellular targets of ZIKV, ZIKV-mediated cell death mechanisms, host cell restriction factors that limit ZIKV replication, and immune evasion mechanisms utilized by ZIKV. Understanding of the mechanisms of ZIKV–host interaction at the cellular level will contribute crucial insights into the development of ZIKV therapeutics and vaccines.

Advances in Zika Virus Host-Cell Interaction: Current Knowledge and Future Perspectives

2019 ◽  
Vol 11 (3) ◽  
pp. 145
Author(s):  
Asawa Priya ◽  
Varshney Naincy ◽  
Gupta Siddhsssarth ◽  
Pandey Vivek ◽  
Singh Manali
Keyword(s):  
Host Cell ◽  
Zika Virus ◽  
Current Knowledge ◽  
Cell Interaction ◽  
Future Perspectives ◽  
Host Cell Interaction

scholarly journals Autophagy Contributes to Host Immunity and Protection against Zika Virus Infection via Type I IFN Signaling

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Yuyi Huang ◽  
Yujie Wang ◽  
Shuhui Meng ◽  
Zhuohang Chen ◽  
Haifan Kong ◽  
...  
Keyword(s):  
Virus Infection ◽  
Cell Line ◽  
Zika Virus ◽  
Fetal Brain ◽  
Host Immunity ◽  
Type I ◽  
Type I Ifn ◽  
Zikv Infection

Recent studies have indicated that the Zika virus (ZIKV) has a significant impact on the fetal brain, and autophagy is contributing to host immune response and defense against virus infection. Here, we demonstrate that ZIKV infection triggered increased LC3 punctuation in mouse monocyte-macrophage cell line (RAW264.7), mouse microglial cell line (BV2), and hindbrain tissues, proving the occurrence of autophagy both in vitro and in vivo. Interestingly, manual intervention of autophagy, like deficiency inhibited by 3-MA, can reduce viral clearance in RAW264.7 cells upon ZIKV infection. Besides, specific siRNA strategy confirmed that autophagy can be activated through Atg7-Atg5 and type I IFN signaling pathway upon ZIKV infection, while knocking down of Atg7 and Atg5 effectively decreased the ZIKV clearance in phagocytes. Furthermore, we analyzed that type I IFN signaling could contribute to autophagic clearance of invaded ZIKV in phagocytes. Taken together, our findings demonstrate that ZIKV-induced autophagy is favorable to activate host immunity, particularly through type I IFN signaling, which participates in host protection and defense against ZIKV infection.

scholarly journals Glial Cells—The Strategic Targets in Amyotrophic Lateral Sclerosis Treatment

2020 ◽  
Vol 9 (1) ◽  
pp. 261 ◽  
Author(s):  
Tereza Filipi ◽  
Zuzana Hermanova ◽  
Jana Tureckova ◽  
Ondrej Vanatko ◽  
Miroslava Anderova
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neurons ◽  
Current Knowledge ◽  
Gene Mutations ◽  
Cell Types ◽  
In Vivo Models ◽  
Cell Therapies ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease, which is characterized by the degeneration of motor neurons in the motor cortex and the spinal cord and subsequently by muscle atrophy. To date, numerous gene mutations have been linked to both sporadic and familial ALS, but the effort of many experimental groups to develop a suitable therapy has not, as of yet, proven successful. The original focus was on the degenerating motor neurons, when researchers tried to understand the pathological mechanisms that cause their slow death. However, it was soon discovered that ALS is a complicated and diverse pathology, where not only neurons, but also other cell types, play a crucial role via the so-called non-cell autonomous effect, which strongly deteriorates neuronal conditions. Subsequently, variable glia-based in vitro and in vivo models of ALS were established and used for brand-new experimental and clinical approaches. Such a shift towards glia soon bore its fruit in the form of several clinical studies, which more or less successfully tried to ward the unfavourable prognosis of ALS progression off. In this review, we aimed to summarize current knowledge regarding the involvement of each glial cell type in the progression of ALS, currently available treatments, and to provide an overview of diverse clinical trials covering pharmacological approaches, gene, and cell therapies.

scholarly journals Animal Models of Zika Virus Infection during Pregnancy

Viruses ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 598 ◽  
Author(s):  
Elizabeth Caine ◽  
Brett Jagger ◽  
Michael Diamond
Keyword(s):  
Animal Models ◽  
Virus Infection ◽  
Zika Virus ◽  
Reproductive Tract ◽  
Congenital Abnormalities ◽  
Tissue Tropism ◽  
Zikv Infection ◽  
In Vivo Models ◽  
Sexually Transmitted

Zika virus (ZIKV) emerged suddenly in the Americas in 2015 and was associated with a widespread outbreak of microcephaly and other severe congenital abnormalities in infants born to mothers infected during pregnancy. Vertical transmission of ZIKV in humans was confirmed when viral RNA was detected in fetal and placental tissues, and this outcome has been recapitulated experimentally in animals. Unlike other flaviviruses, ZIKV is both arthropod- and sexually-transmitted, and has a broad tissue tropism in humans, including multiple tissues of the reproductive tract. The threats posed by ZIKV have prompted the development of multiple in vivo models to better understand the pathogenesis of ZIKV, particularly during pregnancy. Here, we review the progress on animal models of ZIKV infection during pregnancy. These studies have generated a foundation of insights into the biology of ZIKV, and provide a means for evaluating vaccines and therapeutics.

scholarly journals N-Methyl-d-Aspartate (NMDA) Receptor Blockade Prevents Neuronal Death Induced by Zika Virus Infection

mBio ◽  
2017 ◽  
Vol 8 (2) ◽  
Author(s):  
Vivian V. Costa ◽  
Juliana L. Del Sarto ◽  
Rebeca F. Rocha ◽  
Flavia R. Silva ◽  
Juliana G. Doria ◽  
...  
Keyword(s):  
Global Health ◽  
Drug Treatment ◽  
Zika Virus ◽  
Neuronal Death ◽  
Neuronal Damage ◽  
Neurological Complications ◽  
Zikv Infection ◽  
Experimental Animals

ABSTRACT Zika virus (ZIKV) infection is a global health emergency that causes significant neurodegeneration. Neurodegenerative processes may be exacerbated by N-methyl-d-aspartate receptor (NMDAR)-dependent neuronal excitoxicity. Here, we have exploited the hypothesis that ZIKV-induced neurodegeneration can be rescued by blocking NMDA overstimulation with memantine. Our results show that ZIKV actively replicates in primary neurons and that virus replication is directly associated with massive neuronal cell death. Interestingly, treatment with memantine or other NMDAR blockers, including dizocilpine (MK-801), agmatine sulfate, or ifenprodil, prevents neuronal death without interfering with the ability of ZIKV to replicate in these cells. Moreover, in vivo experiments demonstrate that therapeutic memantine treatment prevents the increase of intraocular pressure (IOP) induced by infection and massively reduces neurodegeneration and microgliosis in the brain of infected mice. Our results indicate that the blockade of NMDARs by memantine provides potent neuroprotective effects against ZIKV-induced neuronal damage, suggesting it could be a viable treatment for patients at risk for ZIKV infection-induced neurodegeneration. IMPORTANCE Zika virus (ZIKV) infection is a global health emergency associated with serious neurological complications, including microcephaly and Guillain-Barré syndrome. Infection of experimental animals with ZIKV causes significant neuronal damage and microgliosis. Treatment with drugs that block NMDARs prevented neuronal damage both in vitro and in vivo. These results suggest that overactivation of NMDARs contributes significantly to the neuronal damage induced by ZIKV infection, and this is amenable to inhibition by drug treatment. IMPORTANCE Zika virus (ZIKV) infection is a global health emergency associated with serious neurological complications, including microcephaly and Guillain-Barré syndrome. Infection of experimental animals with ZIKV causes significant neuronal damage and microgliosis. Treatment with drugs that block NMDARs prevented neuronal damage both in vitro and in vivo. These results suggest that overactivation of NMDARs contributes significantly to the neuronal damage induced by ZIKV infection, and this is amenable to inhibition by drug treatment.

scholarly journals Mechanisms and controversies in mutant Cul3-mediated familial hyperkalemic hypertension

2018 ◽  
Vol 314 (5) ◽  
pp. F915-F920 ◽  
Author(s):  
Mohammed Z. Ferdaus ◽  
James A. McCormick
Keyword(s):  
Current Knowledge ◽  
Complex Problem ◽  
Severe Form ◽  
In Vivo Models ◽  
Cullin 3 ◽  
Exon 9 ◽  
Altered Form ◽  
Familial Hyperkalemic Hypertension

Autosomal dominant mutations in cullin-3 ( Cul3) cause the most severe form of familial hyperkalemic hypertension (FHHt). Cul3 mutations cause skipping of exon 9, which results in an internal deletion of 57 amino acids from the CUL3 protein (CUL3-∆9). The precise mechanism by which this altered form of CUL3 causes FHHt is controversial. CUL3 is a member of the cullin-RING ubiquitin ligase family that mediates ubiquitination and thus degradation of cellular proteins, including with-no-lysine [K] kinases (WNKs). In CUL3-∆9-mediated FHHt, proteasomal degradation of WNKs is abrogated, leading to overactivation of the WNK targets sterile 20/SPS-1 related proline/alanine-rich kinase and oxidative stress-response kinase-1, which directly phosphorylate and activate the thiazide-sensitive Na+-Cl− cotransporter. Several groups have suggested different mechanisms by which CUL3-∆9 causes FHHt. The majority of these are derived from in vitro data, but recently the Kurz group (Schumacher FR, Siew K, Zhang J, Johnson C, Wood N, Cleary SE, Al Maskari RS, Ferryman JT, Hardege I, Figg NL, Enchev R, Knebel A, O’Shaughnessy KM, Kurz T. EMBO Mol Med 7: 1285–1306, 2015) described the first mouse model of CUL3-∆9-mediated FHHt. Analysis of this model suggested that CUL3-∆9 is degraded in vivo, and thus Cul3 mutations cause FHHt by inducing haploinsufficiency. We recently directly tested this model but found that other dominant effects of CUL3-∆9 must contribute to the development of FHHt. In this review, we focus on our current knowledge of CUL3-∆9 action gained from in vitro and in vivo models that may help unravel this complex problem.

scholarly journals Epithelial-stromal cell interactions and ECM mechanics drive the formation of airway-mimetic tubular morphology in lung organoids

2020 ◽  
Author(s):  
Tankut G. Guney ◽  
Alfonso Muinelo Herranz ◽  
Sharon Mumby ◽  
Iain E Dunlop ◽  
Ian M Adcock
Keyword(s):  
Epithelial Cell ◽  
Stromal Cells ◽  
Stromal Cell ◽  
Cell Interaction ◽  
Airway Smooth Muscle Cells ◽  
In Vivo Models ◽  
And Function ◽  
Air Liquid Interface

The complex cellular organisation of the human airway tract where interaction between epithelial and stromal lineages and the extracellular matrix (ECM) make it a difficult organ to study in vitro. Current in vitro lung models focus on modelling the lung epithelium such as air-liquid interface (ALI) cultures and bronchospheres, do not model the complex morphology and the cell-ECM interaction seen in vivo. Models that include stromal populations often separate them via a semipermeable barrier, which precludes the effect of cell-cell interaction or do not include the ECM or the effect of ECM mechanics such as viscoelasticity and stiffness. Here we investigated the effect of stromal cells on basal epithelial cell-derived bronchosphere structure and function through a triple culture of bronchial epithelial, lung fibroblast and airway smooth muscle cells. Epithelial-stromal cross talk enabled formation of epithelial cell-driven branching tubules consisting of luminal epithelial cells surrounded by stromal cells termed bronchotubules. Addition of agarose to the Matrigel scaffold (Agrigel) created a mechanically tunable ECM, where viscoelasticity and stiffness could be altered to enable long term tubule survival. Bronchotubule models enable the investigation of how epithelial-stromal cell and cell-ECM communication drive tissue patterning, repair and development of disease.

scholarly journals Improved enzyme-linked immunoadsorbent assay (ELISA) for the study of Trypanosoma cruzi-host cell interaction in vitro

1993 ◽  
Vol 88 (2) ◽  
pp. 235-241 ◽  
Author(s):  
Mauricio R. M. P. Luz ◽  
Maria de Nazaré C. Soeiro ◽  
Tania C. Araújo-Jorge
Keyword(s):  
Trypanosoma Cruzi ◽  
Host Cell ◽  
Cell Interaction ◽  
Host Cell Interaction

scholarly journals The biology of cutaneous neurofibromas

Neurology ◽  
2018 ◽  
Vol 91 (2 Supplement 1) ◽  
pp. S14-S20 ◽  
Author(s):  
Jean-Philippe Brosseau ◽  
Dominique C. Pichard ◽  
Eric H. Legius ◽  
Pierre Wolkenstein ◽  
Robert M. Lavker ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Research Priorities ◽  
Future Research ◽  
In Vivo Models ◽  
Cells Of Origin ◽  
Group Members ◽  
Multiple Levels

ObjectiveA group of experts in dermatology, genetics, neuroscience, and regenerative medicine collaborated to summarize current knowledge on the defined factors contributing to cutaneous neurofibroma (cNF) development and to provide consensus recommendations for future research priorities to gain an improved understanding of the biology of cNF.MethodsThe group members reviewed published and unpublished data on cNF and related diseases via literature search, defined a set of key topic areas deemed critical in cNF pathogenesis, and developed recommendations in a series of consensus meetings.ResultsFive specific topic areas were identified as being relevant to providing an enhanced understanding of the biology of cNF: (1) defining the human cells of origin; (2) understanding the role of the microenvironment, focusing on neurons, mast cells, and fibroblasts; (3) defining the genetic and molecular differences between the cNFs, focusing on size and number; (4) understanding if sex hormones are critical for cNF development or progression; and (5) identifying challenges in establishing in vitro and in vivo models representing human cNF.ConclusionsThe complexity of cNF biology stems from its heterogeneity at multiple levels including genetic, spatial involvement, temporal development, and cellular composition. We propose a unified working model for cNF that builds a framework to address the key questions about cNF that, when answered, will provide the necessary understanding of cNF biology to allow meaningful development of therapies.

scholarly journals Akt Inhibitor MK2206 Prevents Influenza pH1N1 Virus InfectionIn Vitro

2014 ◽  
Vol 58 (7) ◽  
pp. 3689-3696 ◽  
Author(s):  
Oxana V. Denisova ◽  
Sandra Söderholm ◽  
Salla Virtanen ◽  
Carina Von Schantz ◽  
Dmitrii Bychkov ◽  
...  
Keyword(s):  
Virus Infection ◽  
Host Cell ◽  
Treatment Options ◽  
Cell Interaction ◽  
Akt Signaling ◽  
Akt Inhibitor ◽  
Prevention And Treatment ◽  
Host Cell Interaction

ABSTRACTThe influenza pH1N1 virus caused a global flu pandemic in 2009 and continues manifestation as a seasonal virus. Better understanding of the virus-host cell interaction could result in development of better prevention and treatment options. Here we show that the Akt inhibitor MK2206 blocks influenza pH1N1 virus infectionin vitro. In particular, at noncytotoxic concentrations, MK2206 alters Akt signaling and inhibits endocytic uptake of the virus. Interestingly, MK2206 is unable to inhibit H3N2, H7N9, and H5N1 viruses, indicating that pH1N1 evolved specific requirements for efficient infection. Thus, Akt signaling could be exploited further for development of better therapeutics against pH1N1 virus.

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