Perturbation of Wound Healing, Cytoskeletal Organization and Cellular Protein Networks during Hazara Virus Infection

Molinas, Andrea; Turkina, Maria V.; Magnusson, Karl‐Eric; Mirazimi, Alì; Vikström, Elena

doi:10.3389/fcell.2017.00098

Cited by 10 publications

(6 citation statements)

References 64 publications

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“…In addition to dsRNA as a component of RNA virus replication complexes (as discussed for dengue virus) [ 44 ], a virus particle itself (shown for herpes simplex virus) can alter migration potential of a cell [ 45 ]. The Hazara virus as an experimental model for Crimean–Congo hemorrhagic fever virus was analyzed on Caco-2 cells in an epithelial wound healing assay [ 46 ]. Comparable to our data on RV infection of epithelial Vero cells, Hazara virus inhibited migration rate and reduced expression of F-actin and several cytoskeleton-associated proteins [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

“…The Hazara virus as an experimental model for Crimean–Congo hemorrhagic fever virus was analyzed on Caco-2 cells in an epithelial wound healing assay [ 46 ]. Comparable to our data on RV infection of epithelial Vero cells, Hazara virus inhibited migration rate and reduced expression of F-actin and several cytoskeleton-associated proteins [ 46 ]. In line with the slight variations identified for RV strains in the wound healing assay, published data on HCMV strains also indicate strain specific differences in virus induced alterations of cellular migratory capacity.…”

Section: Discussionmentioning

confidence: 99%

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Alterations in Cell Mechanics by Actin Cytoskeletal Changes Correlate with Strain-Specific Rubella Virus Phenotypes for Cell Migration and Induction of Apoptosis

Kräter

Sapudom

Bilz

et al. 2018

Cells

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The cellular cytoskeleton is central for key cellular functions, and as such is a marker for diseased and infected cell states. Here we analyzed infection with rubella virus (RV) strains with respect to phenotypes in cellular mechanical properties, cell movement, and viral cytopathogenicity. Real-time deformability cytometry (RT-DC), as a high-throughput platform for the assessment of cell mechanics, revealed a correlation of an increase in cortical filamentous-actin (F-actin) with a higher cellular stiffness. The additional reduction of stress fibers noted for only some RV strains as the most severe actin rearrangement lowered cell stiffness. Furthermore, a reduced collective and single cell migration speed in a wound healing assay was detected in addition to severe changes in cell morphology. The latter was followed by activation of caspase 3/7 as a sign for induction of apoptosis. Our study emphasizes RT-DC technology as a sensitive means to characterize viral cell populations and to implicate alterations of cell mechanical properties with cell functions. These interdependent events are not only promising options to elucidate viral spread and to understand viral pathologies within the infected host. They also contribute to any diseased cell state, as exemplified by RV as a representative agent for cytoskeletal alterations involved in a cytopathological outcome.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Alterations in Cell Mechanics by Actin Cytoskeletal Changes Correlate with Strain-Specific Rubella Virus Phenotypes for Cell Migration and Induction of Apoptosis

Kräter

Sapudom

Bilz

et al. 2018

Cells

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“…Database searches and label-free quantification. Database searches and label-free quantification (LFQ) were performed as described previously [80][81][82] . Raw files were searched using Sequest HT in Proteome Discoverer (Thermo; version 1.4.0.288) and X!…”

Section: Lc-ms/ms Analysismentioning

confidence: 99%

Oligomeric amyloid-β induces early and widespread changes to the proteome in human iPSC-derived neurons

Sackmann

Hallbeck

2020

Sci Rep

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Alzheimer's disease (AD) is the most common form of dementia globally and is characterized by aberrant accumulations of amyloid-beta (Aβ) and tau proteins. oligomeric forms of these proteins are believed to be most relevant to disease progression, with oligomeric amyloid-β (oAβ) particularly implicated in AD. oAβ pathology spreads among interconnected brain regions, but how oAβ induces pathology in these previously unaffected neurons requires further study. Here, we use well characterized ipSc-derived human neurons to study the early changes to the proteome and phosphoproteome after 24 h exposure to oAβ 1-42. Using nLC-MS/MS and label-free quantification, we identified several proteins that are differentially regulated in response to acute oAβ challenge. At this early timepoint, oAβ induced the decrease of TDP-43, heterogeneous nuclear ribonucleoproteins (hnRNPs), and coatomer complex I (COPI) proteins. Conversely, increases were observed in 20 S proteasome subunits and vesicle associated proteins VAMP1/2, as well as the differential phosphorylation of tau at serine 208. These changes show that there are widespread alterations to the neuronal proteome within 24 h of oAβ uptake, including proteins previously not shown to be related to neurodegeneration. this study provides new targets for the further study of early mediators of AD pathogenesis.Alzheimer's disease (AD) is the most prevalent form of dementia globally and is expected to grow substantially along with the aging global population. Much of the research in this field has focused on the pathological hallmarks of AD, amyloid-β (Aβ) and tau, but the way in which these mediators initiate neuronal pathogenesis at the molecular level requires further understanding. An important consideration in the study of AD is the different properties of Aβ assemblies: monomers, oligomers and fibrils. In particular, there is growing evidence to suggest that low molecular weight Aβ oligomers (oAβ) and protofibrils seed the aggregation of naïve Aβ, confer neurotoxicity, and also correlate to cognitive decline, as reviewed in 1-4 . Much of our current understanding of AD comes from the study of long-term exposure to Aβ in animal models, which has provided valuable insight into the effects of chronic exposure to Aβ, but often overlook the initial steps involved in pathogenesis. In order to further our understanding of the acute effects of exposure to oAβ, we challenged human iPSC-derived neurons with oAβ for 24 h and examined the changes to the proteome and phosphoproteome elicited by this acute oAβ treatment. In this way, we aim to elucidate some of the early effects elicited by oAβ upon neurons.During AD, widespread changes occur in the proteome, including the up-and downregulation of disease-related proteins as well as the post-translational modification (PTM) of proteins. PTMs such as phosphorylation greatly affect the function of proteins and are well known to be important for the pathogenesis of neurodegenerative disorders, where detection of phosphorylated proteins are us...

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“…Peptides were separated by reverse phase chromatography at a flow rate of 300 nl/min on EASY-nLC II (Thermo Scientific). Automated online analyses were performed in positive mode by LTQ Orbitrap Velos Pro hybrid mass spectrometer (Thermo Scientific) as described previously (22). Generated files were analyzed using Sequest HT in Proteome Discoverer (Thermo Fisher Scientific, San Jose, USA, v. 1.4.0.288) using Uniprot database for Homo sapiens and searched with a fragment ion mass tolerance of 0.50 Da and parent ion tolerance of 6.0 ppm.…”

Section: Proteome Analysis By Liquid Chromatography-mass Spectrometrymentioning

confidence: 99%

Lysine in Combination With Estradiol Promote Dissemination of Estrogen Receptor Positive Breast Cancer via Upregulation of U2AF1 and RPN2 Proteins

et al. 2020

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The majority of estrogen receptor positive (ER+) breast cancer (BC) maintain the ER at metastatic sites. Despite anti-estrogen therapy, almost 30% of ER+ BC patients relapse. Thus, new therapeutic targets for ER+ BC are needed. Amino acids (AAs) may affect the metastatic capacity by affecting inflammatory cells. Essential AAs (EAAs) cannot be produced by human cells and might therefore be targetable as therapeutics. Here we sampled extracellular EAAs in vivo by microdialysis in human BC. Mass spectrometry-based proteomics was used to identify proteins affected after EAA and estradiol (E2) exposure to BC cells. Proteins relevant for patient survival were identified, knocked down in BC cells, and metastatic capability was determined in vivo in the transgenic zebrafish model. We found that lysine was the most utilized EAA in human ER+BC in vivo. In zebrafish, lysine in presence of E2 increased neutrophil-dependent dissemination of ER+ BC cells via upregulation of U2AF1 and RPN2 proteins, which both correlated with poor prognosis of ER+ BC patients in clinical databases. Knockdown of U2AF1 and RPN2 decreased the expression of several cell-adhesion molecules resulting in diminished dissemination. Dietary lysine or its related metabolic pathways may be useful therapeutic targets in ER+ BC.

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Perturbation of Wound Healing, Cytoskeletal Organization and Cellular Protein Networks during Hazara Virus Infection

Cited by 10 publications

References 64 publications

Alterations in Cell Mechanics by Actin Cytoskeletal Changes Correlate with Strain-Specific Rubella Virus Phenotypes for Cell Migration and Induction of Apoptosis

Alterations in Cell Mechanics by Actin Cytoskeletal Changes Correlate with Strain-Specific Rubella Virus Phenotypes for Cell Migration and Induction of Apoptosis

Oligomeric amyloid-β induces early and widespread changes to the proteome in human iPSC-derived neurons

Lysine in Combination With Estradiol Promote Dissemination of Estrogen Receptor Positive Breast Cancer via Upregulation of U2AF1 and RPN2 Proteins

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