scholarly journals Highly efficient intercellular spreading of protein misfolding mediated by viral ligand-receptor interactions

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shu Liu ◽  
André Hossinger ◽  
Stefanie-Elisabeth Heumüller ◽  
Annika Hornberger ◽  
Oleksandra Buravlova ◽  
...  
Keyword(s):  
Protein Misfolding ◽  
Viral Infections ◽  
Seed Transmission ◽  
Cell Contact ◽  
Receptor Ligand ◽  
Cellular Models ◽  
Receptor Interactions ◽  
Ligand Interactions ◽  
Direct Cell ◽  
Vesicular Stomatitis

AbstractProtein aggregates associated with neurodegenerative diseases have the ability to transmit to unaffected cells, thereby templating their own aberrant conformation onto soluble homotypic proteins. Proteopathic seeds can be released into the extracellular space, secreted in association with extracellular vesicles (EV) or exchanged by direct cell-to-cell contact. The extent to which each of these pathways contribute to the prion-like spreading of protein misfolding is unclear. Exchange of cellular cargo by both direct cell contact or via EV depends on receptor-ligand interactions. We hypothesized that enabling these interactions through viral ligands enhances intercellular proteopathic seed transmission. Using different cellular models propagating prions or pathogenic Tau aggregates, we demonstrate that vesicular stomatitis virus glycoprotein and SARS-CoV-2 spike S increase aggregate induction by cell contact or ligand-decorated EV. Thus, receptor-ligand interactions are important determinants of intercellular aggregate dissemination. Our data raise the possibility that viral infections contribute to proteopathic seed spreading by facilitating intercellular cargo transfer.

scholarly journals Highly efficient intercellular spreading of protein misfolding mediated by viral ligand - receptor interactions

2020 ◽  
Author(s):  
Shu Liu ◽  
Andre Hossinger ◽  
Annika Hornberger ◽  
Oleksandra Buravlova ◽  
Stephan Müller ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Protein Misfolding ◽  
Protein Aggregates ◽  
Cell Contact ◽  
List Type ◽  
Viral Glycoprotein ◽  
Receptor Ligand ◽  
Cellular Models ◽  
Ligand Interactions ◽  
Direct Cell

SUMMARYPathological protein aggregates associated with neurodegenerative diseases have the ability to transmit to unaffected cells, thereby templating their own aberrant conformation onto soluble proteins of the same kind. Proteopathic seeds can be released into the extracellular space, secreted in association with extracellular vesicles (EV) or exchanged by direct cell-to-cell contact. The extent to which each of these pathways contributes to the prion-like spreading of protein misfolding is unclear. Exchange of cellular cargo by both direct cell-to-cell contact as well as via EV depends on receptor-ligand interactions and subsequent release of cargo into the cytosol. We hypothesized that enabling these interactions through viral ligands enhances the aggregate-inducing capacity of EV-associated proteopathic seeds. Using different cellular models propagating model prion-like protein aggregates, mouse-adapted prions or pathogenic Tau aggregates, we demonstrate that vesicular stomatitis virus glycoprotein and SARS-CoV-2 spike S increase protein aggregate induction by direct cell-to-cell contact or via viral glycoprotein-decorated EV. Thus, receptor-ligand interactions are major determinants of intercellular aggregate dissemination. Further, our data raise the intriguing possibility that acute or latent viral infections contribute to proteopathic seed spreading by facilitating intercellular cargo transfer.HIGHLIGHTSDifferent types of proteopathic seeds are secreted in association with extracellular vesiclesReceptor-ligand interactions are important drivers of direct cell-to-cell and extracellular vesicle-mediated spreading of protein misfoldingViral glycoproteins mediating attachment and membrane fusion strongly enhance aggregate inducing capacity in recipient cellsGRAPHICAL ABSTRACT

scholarly journals Combined radiolabel-binding and immunocytochemical evaluation of receptor–ligand interactions. Studies of transferrin receptors on activated lymphocytes

1981 ◽  
Vol 200 (1) ◽  
pp. 173-176 ◽  
Author(s):  
Gillian M. P. Galbraith ◽  
Robert M. Galbraith
Keyword(s):  
Transferrin Receptor ◽  
Transferrin Receptors ◽  
Receptor Ligand ◽  
Activated Lymphocytes ◽  
Sources Of Error ◽  
Composite Approach ◽  
Receptor Interactions ◽  
Potential Sources ◽  
Ligand Interactions

A protocol that involved both immunohistological and radiolabel-binding procedures was devised for the study of transferrin–receptor interactions. This composite approach yielded considerably more information than did either technique used alone, and also provided a simple means for exclusion of several common potential sources of error.

Modulation of Platelet Activation by Native DNA – Initial Description of Platelet Receptor Type, Number and Discrimination for Native DNA

1981 ◽  
Vol 45 (03) ◽  
pp. 263-266 ◽  
Author(s):  
B A Fiedel ◽  
M E Frenzke
Keyword(s):  
Platelet Aggregation ◽  
Human Platelets ◽  
Scatchard Analysis ◽  
Type Number ◽  
Single Class ◽  
Receptor Ligand ◽  
Platelet Receptor ◽  
Platelet Binding ◽  
Ligand Interactions ◽  
Initial Description

SummaryNative DNA (dsDNA) induces the aggregation of isolated human platelets. Using isotopically labeled dsDNA (125I-dsDNA) and Scatchard analysis, a single class of platelet receptor was detected with a KD = 190 pM and numbering ~275/platelet. This receptor was discriminatory in that heat denatured dsDNA, poly A, poly C, poly C · I and poly C · poly I failed to substantially inhibit either the platelet binding of, or platelet aggregation induced by, dsDNA; by themselves, these polynucleotides were ineffective as platelet agonists. However, poly G, poly I and poly G · I effectively and competitively inhibited platelet binding of the radioligand, independently activated the platelet and when used at a sub-activating concentration decreased the extent of dsDNA stimulated platelet aggregation. These data depict a receptor on human platelets for dsDNA and perhaps certain additional polynucleotides and relate receptor-ligand interactions to a physiologic platelet function.

scholarly journals Mechanisms that allow vaccination against an oncolytic vesicular stomatitis virus-encoded transgene to enhance safety without abrogating oncolysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Amanda W. K. AuYeung ◽  
Robert C. Mould ◽  
Ashley A. Stegelmeier ◽  
Jacob P. van Vloten ◽  
Khalil Karimi ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Vesicular Stomatitis Virus ◽  
Cell Response ◽  
Viral Infections ◽  
T Cell Response ◽  
Oncolytic Viruses ◽  
Oncolytic Virotherapy ◽  
Cell Immunity ◽  
Vesicular Stomatitis

AbstractVaccination can prevent viral infections via virus-specific T cells, among other mechanisms. A goal of oncolytic virotherapy is replication of oncolytic viruses (OVs) in tumors, so pre-existing T cell immunity against an OV-encoded transgene would seem counterproductive. We developed a treatment for melanomas by pre-vaccinating against an oncolytic vesicular stomatitis virus (VSV)-encoded tumor antigen. Surprisingly, when the VSV-vectored booster vaccine was administered at the peak of the primary effector T cell response, oncolysis was not abrogated. We sought to determine how oncolysis was retained during a robust T cell response against the VSV-encoded transgene product. A murine melanoma model was used to identify two mechanisms that enable this phenomenon. First, tumor-infiltrating T cells had reduced cytopathic potential due to immunosuppression. Second, virus-induced lymphopenia acutely removed virus-specific T cells from tumors. These mechanisms provide a window of opportunity for replication of oncolytic VSV and rationale for a paradigm change in oncolytic virotherapy, whereby immune responses could be intentionally induced against a VSV-encoded melanoma-associated antigen to improve safety without abrogating oncolysis.

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