scholarly journals Tyro3 Family-Mediated Cell Entry of Ebola and Marburg Viruses

2006 ◽  
Vol 80 (20) ◽  
pp. 10109-10116 ◽  
Author(s):  
Masayuki Shimojima ◽  
Ayato Takada ◽  
Hideki Ebihara ◽  
Gabriele Neumann ◽  
Kouki Fujioka ◽  
...  
Keyword(s):  
Receptor Tyrosine Kinase ◽  
Molecular Mechanisms ◽  
Family Members ◽  
Ectopic Expression ◽  
Hemorrhagic Fever ◽  
Cell Types ◽  
Lymphoid Cells ◽  
Cell Entry ◽  
A Cell ◽  
Receptor Tyrosine Kinase Family

ABSTRACT Filoviruses, represented by the genera Ebolavirus and Marburgvirus, cause a lethal hemorrhagic fever in humans and in nonhuman primates. Although filovirus can replicate in various tissues or cell types in these animals, the molecular mechanisms of its broad tropism remain poorly understood. Here we show the involvement of members of the Tyro3 receptor tyrosine kinase family—Axl, Dtk, and Mer—in cell entry of filoviruses. Ectopic expression of these family members in lymphoid cells, which otherwise are highly resistant to filovirus infection, enhanced infection by pseudotype viruses carrying filovirus glycoproteins on their envelopes. This enhancement was reduced by antibodies to Tyro3 family members, Gas6 ligand, or soluble ectodomains of the members. Live Ebola viruses infected both Axl- and Dtk-expressing cells more efficiently than control cells. Antibody to Axl inhibited infection of pseudotype viruses in a number of Axl-positive cell lines. These results implicate each Tyro3 family member as a cell entry factor in filovirus infection.

scholarly journals The Phosphatidylserine Receptor TIM-1 Enhances Authentic Chikungunya Virus Cell Entry

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1828
Author(s):  
Jared Kirui ◽  
Yara Abidine ◽  
Annasara Lenman ◽  
Koushikul Islam ◽  
Yong-Dae Gwon ◽  
...  
Keyword(s):  
Chikungunya Virus ◽  
Molecular Mechanisms ◽  
Rna Virus ◽  
Ectopic Expression ◽  
Point Mutations ◽  
Cell Entry ◽  
Target Cells ◽  
Human Hepatoma Cells ◽  
Chikv Infection ◽  
Phosphatidylserine Receptor

Chikungunya virus (CHIKV) is a re-emerging, mosquito-transmitted, enveloped positive stranded RNA virus. Chikungunya fever is characterized by acute and chronic debilitating arthritis. Although multiple host factors have been shown to enhance CHIKV infection, the molecular mechanisms of cell entry and entry factors remain poorly understood. The phosphatidylserine-dependent receptors, T-cell immunoglobulin and mucin domain 1 (TIM-1) and Axl receptor tyrosine kinase (Axl), are transmembrane proteins that can serve as entry factors for enveloped viruses. Previous studies used pseudoviruses to delineate the role of TIM-1 and Axl in CHIKV entry. Conversely, here, we use the authentic CHIKV and cells ectopically expressing TIM-1 or Axl and demonstrate a role for TIM-1 in CHIKV infection. To further characterize TIM-1-dependent CHIKV infection, we generated cells expressing domain mutants of TIM-1. We show that point mutations in the phosphatidylserine binding site of TIM-1 lead to reduced binding, entry, and infection of CHIKV. Ectopic expression of TIM-1 renders immortalized keratinocytes permissive to CHIKV, whereas silencing of endogenously expressed TIM-1 in human hepatoma cells reduces CHIKV infection. Altogether, our findings indicate that, unlike Axl, TIM-1 readily promotes the productive entry of authentic CHIKV into target cells.

scholarly journals Hyaluronate can function as a cell adhesion molecule and CD44 participates in hyaluronate recognition.

1990 ◽  
Vol 172 (1) ◽  
pp. 69-75 ◽  
Author(s):  
K Miyake ◽  
C B Underhill ◽  
J Lesley ◽  
P W Kincade
Keyword(s):  
Cell Adhesion ◽  
Stromal Cells ◽  
Divalent Cations ◽  
Cell Types ◽  
Lymphoid Cells ◽  
Hybridoma Cells ◽  
Antibody Treatment ◽  
A Cell ◽  
Adhesive Interactions ◽  
Potential Ligand

A cell adhesion model was previously used to select a series of monoclonal antibodies (mAbs), which were subsequently found to recognize CD44/Pgp-1. Interest in these reagents increased with the finding that they totally inhibited production of lymphoid or myeloid cells in long-term bone marrow cultures. Further investigation has now revealed that hyaluronate is a potential ligand for CD44 and that hyaluronate recognition accounts for the adhesion between B lineage hybridoma and stromal cells. The hybridoma cells adhered to hyaluronate-coated plastic wells as well as to monolayers of stromal cells. The adhesion in both cases was inhibited by treatment with hyaluronidases, and did not require divalent cations. Addition of exogenous hyaluronate also diminished binding of lymphoid cells to stromal cells. One of several mAbs to Pgp-1/CD44 was particularly effective at blocking these interactions. Since hyaluronate and Pgp-1/CD44 were present on both cell types, experiments were done to determine the cellular location of interacting molecules required for the adhesion process. Treatment of lymphoid cells with an anti-Pgp-1/CD44 antibody was more inhibitory than antibody treatment of the stromal cells. Conversely, hyaluronidase treatment of stromal cells reduced subsequent binding more than treatment of the lymphoid cells. Adhesive interactions that involve hyaluronate and CD44 could contribute to a number of cell recognition processes, including ones required for normal lympho-hemopoiesis.

scholarly journals Profiling of Primary and Mature miRNA Expression in Atherosclerosis Associated Cell Types

2021 ◽  
Author(s):  
Pierre R. Moreau ◽  
Vanesa Tomas Bosch ◽  
Maria Bouvy-Liivrand ◽  
Kadri Õunap ◽  
Tiit Örd ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Molecular Mechanisms ◽  
Umbilical Vein ◽  
Cell Types ◽  
Integrative Approach ◽  
Dependent Manner ◽  
Cell Type ◽  
A Cell ◽  
Cell Type Specific

Objective: Atherosclerosis is the underlying cause of most cardiovascular diseases. The main cell types associated with disease progression in the vascular wall are endothelial cells, smooth muscle cells, and macrophages. Although their role in atherogenesis has been extensively described, molecular mechanisms underlying gene expression changes remain unknown. The objective of this study was to characterize microRNA (miRNA)-related regulatory mechanisms taking place in the aorta during atherosclerosis: Approach and Results: We analyzed the changes in primary human aortic endothelial cells and human umbilical vein endothelial cell, human aortic smooth muscle cell, and macrophages (CD14+) under various proatherogenic stimuli by integrating GRO-seq, miRNA-seq, and RNA-seq data. Despite the highly cell-type-specific expression of multi-variant pri-miRNAs, the majority of mature miRNAs were found to be common to all cell types and dominated by 2 to 5 abundant miRNA species. We demonstrate that transcription contributes significantly to the mature miRNA levels although this is dependent on miRNA stability. An analysis of miRNA effects in relation to target mRNA pools highlighted pathways and targets through which miRNAs could affect atherogenesis in a cell-type-dependent manner. Finally, we validate miR-100-5p as a cell-type specific regulator of inflammatory and HIPPO-YAP/TAZ-pathways. Conclusions: This integrative approach allowed us to characterize miRNA dynamics in response to a proatherogenic stimulus and identify potential mechanisms by which miRNAs affect atherogenesis in a cell-type-specific manner.

scholarly journals How a cell decides its own fate: a single-cell view of molecular mechanisms and dynamics of cell-type specification

2021 ◽  
Author(s):  
Maria Mircea ◽  
Stefan Semrau
Keyword(s):  
Single Cell ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Lineage Tracing ◽  
Molecular Profile ◽  
Cell Type ◽  
Molecular Changes ◽  
Starting Point ◽  
A Cell ◽  
Type Specification

On its path from a fertilized egg to one of the many cell types in a multicellular organism, a cell turns the blank canvas of its early embryonic state into a molecular profile fine-tuned to achieve a vital organismal function. This remarkable transformation emerges from the interplay between dynamically changing external signals, the cell's internal, variable state, and tremendously complex molecular machinery; we are only beginning to understand. Recently developed single-cell omics techniques have started to provide an unprecedented, comprehensive view of the molecular changes during cell-type specification and promise to reveal the underlying gene regulatory mechanism. The exponentially increasing amount of quantitative molecular data being created at the moment is slated to inform predictive, mathematical models. Such models can suggest novel ways to manipulate cell types experimentally, which has important biomedical applications. This review is meant to give the reader a starting point to participate in this exciting phase of molecular developmental biology. We first introduce some of the principal molecular players involved in cell-type specification and discuss the important organizing ability of biomolecular condensates, which has been discovered recently. We then review some of the most important single-cell omics methods and relevant findings they produced. We devote special attention to the dynamics of the molecular changes and discuss methods to measure them, most importantly lineage tracing. Finally, we introduce a conceptual framework that connects all molecular agents in a mathematical model and helps us make sense of the experimental data.

scholarly journals IL-10-Producing ILCs: Molecular Mechanisms and Disease Relevance

2021 ◽  
Vol 12 ◽  
Author(s):  
Hui Sun ◽  
Yuzhang Wu ◽  
Yi Zhang ◽  
Bing Ni
Keyword(s):  
Nk Cells ◽  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Cell Types ◽  
Interleukin 10 ◽  
Vital Role ◽  
Lymphoid Cells ◽  
Stable Production ◽  
Disease Relevance ◽  
And Function

Innate lymphoid cells (ILCs) are mainly composed of natural killer (NK) cells and helper-like lymphoid cells, which play a vital role in maintaining tissue homeostasis, enhancing adaptive immunity and regulating tissue inflammation. Alteration of the distribution and function of ILCs subgroups are closely related to the pathogenesis of inflammatory diseases and cancers. Interleukin-10 (IL-10) is a highly pleiotropic cytokine, and can be secreted by several cell types, among of which ILCs are recently verified to be a key source of IL-10. So far, the stable production of IL-10 can only be observed in certain NK subsets and ILC2s. Though the regulatory mechanisms for ILCs to produce IL-10 are pivotal for understanding ILCs and potential intervenes of diseases, which however is largely unknown yet. The published studies show that ILCs do not share exactly the same mechanisms for IL-10 production with helper T cells. In this review, the molecular mechanisms regulating IL-10 production in NK cells and ILC2s are discussed in details for the first time, and the role of IL-10-producing ILCs in diseases such as infections, allergies, and cancers are summarized.

scholarly journals A molecular logic of sensory coding revealed by optical tagging of physiologically-defined neuronal types

2019 ◽  
Author(s):  
Donghoon Lee ◽  
Maiko Kume ◽  
Timothy E Holy
Keyword(s):  
Neural Circuit ◽  
Strong Predictor ◽  
Ectopic Expression ◽  
Cell Types ◽  
Specific Cell ◽  
Molecular Logic ◽  
Neuronal Types ◽  
A Cell ◽  
Circuit Function

Neural circuit analysis relies on having molecular markers for specific cell types. However, for a cell type identified only by its circuit function, the process of identifying markers remains laborious. Here, we report physiological optical tagging sequencing (PhOTseq), a technique for tagging and expression-profiling cells based on their functional properties. We demonstrate that PhOTseq is capable of selecting rare cell types and enriching them by nearly one hundred-fold. We applied PhOTseq to the challenge of mapping receptor-ligand pairings among vomeronasal pheromone-sensing neurons in mice. Together with in vivo ectopic expression of vomeronasal chemoreceptors, PhOTseq identified the complete combinatorial receptor code for a specific set of ligands, and revealed that the primary sequence of a chemoreceptor was an unexpectedly strong predictor of functional similarity.

scholarly journals Rational reprogramming of cellular states by combinatorial perturbation

2018 ◽  
Author(s):  
Jialei Duan ◽  
Boxun Li ◽  
Minoti Bhakta ◽  
Shiqi Xie ◽  
Pei Zhou ◽  
...  
Keyword(s):  
Computational Analysis ◽  
Ectopic Expression ◽  
Cell Types ◽  
Specific Cell ◽  
Cell Type ◽  
Epicardial Cells ◽  
Organ Specific ◽  
A Cell ◽  
Cardiac System ◽  
Combinatorial Space

AbstractEctopic expression of transcription factors (TFs) can reprogram cell state. However, due to the large combinatorial space of possible TF cocktails, it remains difficult to identify TFs that reprogram specific cell types. Here, we develop Reprogram-Seq to experimentally screen thousands of TF cocktails for reprogramming performance. Reprogram-Seq leverages organ-specific cell atlas data with single-cell perturbation and computational analysis to predict, evaluate, and optimize TF combinations that reprogram a cell type of interest. Focusing on the cardiac system, we perform Reprogram-Seq on MEFs using an undirected library of 48 cardiac factors and separately on a directed library of 10 epicardial-related TFs. We identify a novel combination of 3 TFs which efficiently reprogram MEFs to epicardial-like cells that are transcriptionally, molecularly, morphologically, and functionally similar to primary epicardial cells. Reprogram-Seq holds promise to accelerate the generation of specific cell types for regenerative medicine.

scholarly journals Mechanistic paradigms of cell death - revisited

2021 ◽  
Vol 42 (4) ◽  
pp. 903-917
Author(s):  
S.V.S. Rana ◽  
Keyword(s):  
Cell Death ◽  
Molecular Mechanisms ◽  
Human Health Risk ◽  
Cell Types ◽  
Enzymatic Antioxidants ◽  
Cellular Targets ◽  
A Cell ◽  
The Impact ◽  
Made In

Present review is the description of a journey that originates from Virchows' cell theory and terminates with the role of molecular switches in cell death recently proposed by Orrenius. Landmark discoveries made, in between, to characterize regulated as well as accidental cell death have also been documented. It embraces the studies that were made in early nineties to understand cellular homeostasis in health and disease. Furthermore, the effects of foreign chemicals on different cell types witnessed in late nineties have been classified into necrosis, apoptosis, autophagy etc. Since it is important to know how a cell dies, studies made in our own and other laboratories on the role of reactive oxygen species, oxidative stress, intracellular Ca2+ homeostasis, redox imbalance, mitochondrial and ER stress in cell death have also been reviewed. Possibility of a cross talk amongst these mechanisms has also been examined. It discusses the impact of wonder molecules like CYP450, GSH, metallothionein and melatonin together with enzymatic and non-enzymatic antioxidants on cell death. Understanding the cellular targets and molecular mechanisms activated by a variety of environmental xenobiotics is fundamental for human health risk assessment. It is expected that the contents of this article will answer the fundamental question- why and how cells die.

scholarly journals Human, Nonhuman Primate, and Bat Cells Are Broadly Susceptible to Tibrovirus Particle Cell Entry

2018 ◽  
Author(s):  
Yingyun Cai ◽  
Shuiqing Yu ◽  
Rohit Jangra ◽  
Elena Postnikova ◽  
Jiro Wada ◽  
...  
Keyword(s):  
Nonhuman Primate ◽  
Phylogenetic Analyses ◽  
Hemorrhagic Fever ◽  
Cell Types ◽  
Cell Entry ◽  
Coastal Plains ◽  
Human Virus ◽  
Mosquito Cells ◽  
Boa Constrictor ◽  
Human Sera

In 2012, the genome of a novel rhabdovirus, Bas-Congo virus, was discovered in the acute-phase serum of a Congolese patient with presumed viral hemorrhagic fever. In the absence of a replicating virus isolate, fulfilling Koch's postulates to determine whether Bas-Congo virus is indeed a human virus and/or pathogen has been impossible. However, experiments with vesiculoviral particles pseudotyped with Bas-Congo glycoprotein suggested that Bas-Congo virus particles can enter cells from multiple animals, including humans. In 2015, genomes of two related viruses, Ekpoma virus 1 and Ekpoma virus 2, were detected in human sera in Nigeria. Isolates could not be obtained. Phylogenetic analyses led to the classification of Bas-Congo virus, Ekpoma virus 1, and Ekpoma virus 2 in the same genus, Tibrovirus, together with five biting midge-borne rhabdoviruses (i.e., Beatrice Hill virus, Bivens Arm virus, Coastal Plains virus, Sweetwater Branch virus, and Tibrogargan virus) not known to infect humans. Using individual recombinant vesiculoviruses expressing the glycoproteins of all eight known tibroviruses and more than 75 cell lines representing different animal species, we demonstrate that the glycoproteins of all tibroviruses can mediate vesiculovirus particle entry into human, bat, nonhuman primate, cotton rat, boa constrictor, and Asian tiger mosquito cells. Using four of five isolated authentic tibroviruses (i.e., Bivens Arm virus, Coastal Plains virus, Sweetwater Branch virus, and Tibrogargan virus), our experiments indicate that many cell types may be partially resistant to tibrovirus replication after virion cell entry. Consequently, experimental data solely obtained from experiments using tibrovirus surrogate systems (e.g., vesiculoviral pseudotypes, recombinant vesiculoviruses) cannot be used to predict whether Bas-Congo virus, or any other tibrovirus, infects humans.

scholarly journals An alternative model for type I interferon induction downstream of human TLR2

2020 ◽  
Vol 295 (42) ◽  
pp. 14325-14342
Author(s):  
Timo Oosenbrug ◽  
Michel J. van de Graaff ◽  
Mariëlle C. Haks ◽  
Sander van Kasteren ◽  
Maaike E. Ressing
Keyword(s):  
Molecular Mechanisms ◽  
Human Monocyte ◽  
Cell Types ◽  
Type I Interferons ◽  
Type I ◽  
Downstream Signaling ◽  
Interferon Stimulated Genes ◽  
Cytokines And Chemokines ◽  
A Cell ◽  
Extracellular Environment

Surface-exposed Toll-like receptors (TLRs) such as TLR2 and TLR4 survey the extracellular environment for pathogens. TLR activation initiates the production of various cytokines and chemokines, including type I interferons (IFN-I). Downstream of TLR4, IFNβ secretion is only vigorously triggered in macrophages when the receptor undergoes endocytosis and switches signaling adaptor; surface TLR4 engagement predominantly induces proinflammatory cytokines via the signaling adaptor MyD88. It is unclear whether this dichotomy is generally applicable to other TLRs, cell types, or differentiation states. Here, we report that diverse TLR2 ligands induce an IFN-I response in human monocyte-like cells, but not in differentiated macrophages. This TLR2-dependent IFN-I signaling originates from the cell surface and depends on MyD88; it involves combined activation of the transcription factors IRF3 and NF-κB, driven by the kinases TBK1 and TAK1-IKKβ, respectively. TLR2-stimulated monocytes produced modest IFNβ levels that caused productive downstream signaling, reflected by STAT1 phosphorylation and expression of numerous interferon-stimulated genes. Our findings reveal that the outcome of TLR2 signaling includes an IFN-I response in human monocytes, which is lost upon macrophage differentiation, and differs mechanistically from IFN-I-induction through TLR4. These findings point to molecular mechanisms tailored to the differentiation state of a cell and the nature of receptors activated to control and limit TLR-triggered IFN-I responses.

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