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Autocatalytic activation of influenza hemagglutinin.

Enveloped viruses contain surface proteins that mediate fusion between the viral and target cell membranes following an activating stimulus. Acidic pH induces the influenza virus fusion protein hemagglutinin (HA) via irreversible refolding of a trimeric conformational state leading to exposure of hydrophobic fusion peptides on each trimer subunit. Herein, we show that cells expressing fowl plague virus HA demonstrate discrete switching behavior with respect to the HA conformational change. Partially activated states do not exist at the scale of the cell, activation of HA leads to aggregation o

Time-resolved single virus tracking and spectral imaging to understand HIV-1 entry and fusion.

Single Virus Tracking (SVT) is a key technique to understand how individual viral particles evolve during the infection cycle. In the case of the human immunodeficiency virus (HIV-1), this technology, which can be employed using a simple and affordable wide-field microscope, has proven to be very useful in the first steps of infection, such as the kinetics of the fusion reaction or the point of fusion within live cells. Here, we describe how SVT in combination with other spectral imaging approaches is a powerful technique to illuminate crucial mechanistic aspects of the HIV-1 fusion reaction.

Neurodegeneration augments the ability of bone marrow-derived mesenchymal stem cells to fuse with Purkinje neurons in Niemann-Pick type C mice.

After transplantation, adult bone marrow-derived mesenchymal stem cells (BM-MSCs) may undergo transdifferentiation and/or cell fusion in response to new environments. However, the mechanism(s) that govern these cell fate switches remain unknown. Here we demonstrate that the pathology associated with murine Niemann-Pick disease type C (NP-C) cerebellum augments the ability of BM-MSCs to fuse with Purkinje neurons. The results suggest that the degenerative microenvironment of Purkinje neurons in the NP-C cerebellum modulates the cell fate switch of BM-MSCs via cell fusion.

Development and evaluation of multiepitope fusion proteins for serological diagnosis of animal brucellosis.

Brucellosis, a zoonotic disease caused by Brucella spp., leads to severe reproductive issues in livestock and economic losses. Current serological diagnostics using lipopolysaccharide (LPS) antigens often exhibit cross-reactivity, reducing diagnostic specificity. This study aimed to develop multiepitope fusion proteins based on Brucella B-cell epitopes using bioinformatics tools and the Immune Epitope Database (IEDB) to enhance diagnostic accuracy. B-cell epitopes from major Brucella outer membrane proteins and other antigenic proteins were predicted using bioinformatics tools (BepiPred, ABCpr

Pan-coronavirus fusion inhibitors possess potent inhibitory activity against HIV-1, HIV-2, and simian immunodeficiency virus.

EK1 peptide is a membrane fusion inhibitor with broad-spectrum activity against human coronaviruses (CoVs). In the outbreak of COVID-19, we … -CoV-2 derived fusion inhibitor lipopeptides (IPB02 ∼ IPB09) also inhibited HIV-1 Env-mediated cell-cell fusion and infection efficiently. In the inhibition of a panel of HIV-1 mutants resistant to HIV-1 fusion inhibitors, EK1V1 and IPB02-based inhibitors exhibited significantly decreased or increased activities, suggesting the heptad repeat-1 region (HR1) of …

Conformational plasticity underlies membrane fusion induced by an HIV sequence juxtaposed to the lipid envelope.

Envelope glycoproteins from genetically-divergent virus families comprise fusion peptides (FPs) that have been posited to insert and perturb the membranes of target cells upon activation of the virus-cell fusion reaction. Conserved sequences rich in aromatic residues juxtaposed to the external leaflet of the virion-wrapping membranes are also frequently found in viral fusion glycoproteins. These membrane-proximal external regions (MPERs) have been implicated in the promotion of the viral membrane restructuring event required for fusion to proceed, hence, proposed to comprise supplementary FPs.…

The Biological Enhancement of Spinal Fusion for Spinal Degenerative Disease.

In this era of aging societies, the number of elderly individuals who undergo spinal arthrodesis for various degenerative diseases is increasing. Poor bone quality and osteogenic ability in older patients, due to osteoporosis, often interfere with achieving bone fusion after spinal arthrodesis. Enhancement of bone fusion requires shifting bone homeostasis toward increased bone formation and reduced resorption. Several biological enhancement strategies of bone formation have been conducted in animal models of spinal arthrodesis and human clinical trials. Pharmacological agents for osteoporosis

Rigid amphipathic fusion inhibitors, small molecule antiviral compounds against enveloped viruses.

Antiviral drugs targeting viral proteins often result in prompt selection for resistance. Moreover, the number of viral targets is limited. Novel antiviral targets are therefore needed. The unique characteristics of fusion between virion envelopes and cell membranes may provide such targets. Like all fusing bilayers, viral envelopes locally adopt hourglass-shaped stalks during the initial stages of fusion, a process that requires local negative membrane curvature. Unlike cellular vesicles, however, viral envelopes do not redistribute lipids between leaflets, can only use the energy released by

Galectin-1 Modulates the Fusogenic Activity of Placental Endogenous Retroviral Envelopes.

Syncytin-1 and -2 are glycoproteins encoded by human endogenous retrovirus (hERV) that, through their fusogenic properties, are needed for the formation of the placental syncytiotrophoblast. Previous studies suggested that these proteins, in addition to the EnvP(b) envelope protein, are also involved in other cell fusion events. Since galectin-1 is a β-galactoside-binding protein associated with cytotrophoblast fusion during placental development, we previously tested its effect on Syncytin-mediated cell fusion and showed that this protein differently modulates the fusogenic potential of Syncy…

Induction of immune responses by a novel recombinant fusion protein of enterovirus A71 in BALB/c mice.

Fusion protein technology is used in biotechnology and medical developments. In this study, recombinant fusion proteins from enterovirus A71 (EV-A71) subgenotype B5, Thailand were designed based two surface proteins (VP1 and VP2) and an internal protein (VP4), and named "VP0" (consisting of VP4-VP2) and "EV71" (consisting of VP4-VP2-VP1), respectively. The recombinant fusion proteins VP0 and EV71 were expressed in insect cells and successfully produced and secreted into the media. Both recombinant fusion proteins were shown to have immunogenic properties in BALB/c mice when formulated with Fre

Antibody-guided enzyme therapy of cancer producing cyanide results in necrosis of targeted cells.

A number of enzyme/prodrug activation approaches for the treatment of cancer have been reported to date with varying success. We describe progress in the development of a system based on a beta-glucosidase enzyme in combination with a naturally occurring "prodrug," the sugar linamarin, which releases the cytotoxin cyanide. A recombinant fusion protein, composed of an scFv (MFE-23) reactive against carcinoembryonic antigen (CEA) and a plant-derived beta-glucosidase (linamarase), was produced and its cytotoxic potential was investigated. The fusion protein was expressed in a supersecretory mutan

Zn2+ depletion blocks endosome fusion.

Fusion among endosomes is an important step for transport and sorting of internalized macromolecules. Working in a cell-free system, we previously reported that endosome fusion requires cytosol and ATP, and is sensitive to N-ethylmaleimide. Fusion is regulated by monomeric and heterotrimeric GTP-binding proteins. We now report that fusion can proceed at very low Ca2+ concentrations, i.e. < 30 nM. Moreover, fusion is not affected when intravesicular Ca2+ is depleted by preincubation of vesicles with calcium ionophores (5 microM ionomycin or A23187) in the presence of calcium chelators (5 mM EGT

HIV-2 and SIV infection of nonprimate cell lines expressing human CD4: restrictions to replication at distinct stages.

Mouse, rat, rabbit, cat, and mink cell lines expressing human CD4 restrict entry of HIV-1 strains at the cell surface. We now report that CD4+ cat and rabbit cell lines are permissive to cell fusion induced by several HIV-2 and SIV strains. CD4+ rat and mouse cells are only sensitive to HIV-2 and SIV fusion in the presence of active amphotericin B. HIV-2 and SIV replicate in CD4+ cat and CD4+ mink cells, but not in the CD4+ rabbit, rat, or mouse cells. These latter cell lines poorly express a transfected DNA molecular clone of HIV-2 DNA. CD4+ rat cells are sensitive to entry by HIV-2 (HTLV-1) …

Inefficient formation of a complex among CXCR4, CD4 and gp120 in U937 clones resistant to X4 gp120-gp41-mediated fusion.

Certain subclones (designated as minus clones) of the promonocytic U937 cell line do not support efficient infection and fusion mediated by T cell line adapted (TCLA) X4 HIV-1 gp120-gp41 (Env) although the CXCR4 and CD4 concentrations at their surfaces are similar to those at the surfaces of clones susceptible to HIV-1 entry (plus clones) (H. Moriuchi et al., J. Virol. 71, 9664-9671, 1997). To test the hypothesis that inefficient formation of gp120-CD4-CXCR4 complexes could contribute to the mechanism of resistance to Env-mediated fusion in the minus clones, we incubated plus and minus cells w

Expression profiles of lncRNAs, miRNAs, and mRNAs and interaction analysis indicate their potential involvement during testicular fusion in Spodoptera litura.

Testicular fusion of Spodoptera litura occures during metamorphosis, which benefits sperms development. Previous research identified involvement of ECM-integrin interaction pathways, MMPs in testicular fusion, but the regulatory mechanism remains unclear. RNA-seq was performed to analyze long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in testes, aiming to uncover potential regulatory mechanisms of testicular fusion. 2150 lncRNAs, 2742 targeted mRNAs, and 347 miRNAs were identified in testes at three different developmental stages. Up-regulated DElncRNAs and DEmRNAs, as well as down-regul

FUSION: a web-based application for in-depth exploration of multi-omics data with brightfield histology.

Spatial technologies examining the cell and tissue microenvironment at near single-cell resolution are revealing important molecular insights. However, few tools enable integrated, interactive analysis of spatial-omics with tissue morphology in the same functional tissue unit. Here, we present FUSION (Functional Unit State Identification in Whole Slide Images), a web-based platform for visualizing and analyzing spatial-omics data with high-resolution histology. FUSION provides workflows for assessing cell compositions, quantitative morphometrics, and comparative tissue analyses. We demonstrate

Effect on fusion induction of point mutations introduced into the F protein of mumps virus.

We have tested the effect of substitution of an amino acid at position 195 of the F protein of mumps virus on cell-to-cell fusion caused by the virus. Introduction of amino acids with aromatic side chains into this position resulted in reduction of fusion induction. Furthermore the F protein was not cleaved when the amino acid at this position was substituted by several amino acids, suggesting that the amino acid at this position was essential to keep the tertiary structure of the protein that might be required not only for proper folding of the protein but also for induction of membrane fusio…

FGFR2 fusion/rearrangement is associated with favorable prognosis and immunoactivation in patients with intrahepatic cholangiocarcinoma.

Increasing evidence highlights that fibroblast growth factor receptor 2 (FGFR2) fusion/rearrangement shows important therapeutic value for patients with intrahepatic cholangiocarcinoma (ICC). This study aims to explore the association of FGFR2 status with the prognosis and immune cell infiltration profiles of patients with ICC. A total of 226 ICC tissue samples from patients who received surgery at the Department of Liver Surgery at Zhongshan Hospital, Fudan University, were collected retrospectively and assigned to a primary cohort (n = 152) and validation cohort (n = 74) group. Fluorescence

Receptor binding and priming of the spike protein of SARS-CoV-2 for membrane fusion.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is initiated by virus binding to the ACE2 cell-surface receptors1-4, followed by fusion of the virus and cell membranes to release the virus genome into the cell. Both receptor binding and membrane fusion activities are mediated by the virus spike glycoprotein5-7. As with other class-I membrane-fusion proteins, the spike protein is post-translationally cleaved, in this case by furin, into the S1 and S2 components that remain associated after cleavage8-10. Fusion activation after receptor binding is proposed to involve

Функции фузогенной и нефузогенной деятельности синцитина-1 в физиологических и патологических процессах человека.

На долю эндогенных ретровирусов человека (ХЕРВ), представляющих генетические остатки древних вирусных инфекций, приходится приблизительно 8% генома человека. Среди белков, закодированных этими вирусами, Синтитин-1, кодируемый геном env семейства HERV-W, функционирует как жизненно важный белок синтеза в плацентальном развитии, в котором он играет ключевую роль в содействии синтезу трофобластных клеток для формирования синцитотрофобласта, который необходим для поддержания структурной целостности и функциональной жизнеспособности плаценты. Недавние исследования показали, что в дополнение к своему

Совпадение в аннотации оригинала
Human endogenous retroviruses (HERVs), which represent the genetic remnants of ancient viral infections, constitute approximately 8 % of the … rogression, and metastasis of tumors, potentially promoting tumor invasion via mechanisms involving cell fusion and modulation of the immune microenvironment. Moreover, associations have been established between Syncytin-1 and neurological disorders, including multiple sclerosis and schizophrenia, in which it modulates neuroinflammation. In this review, we sy …