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Изоформы CADM1 и CADM2 с короткометогенными корями Neurothogenic Meambrane Fusion на основе взаимодействия с вирусом Hemagglutiin.

Вирус кори (MeV), покрытый вирусом РНК в семействе Paramyxoviridae, обычно вызывает острые фебрилические заболевания с сыпью кожи, но в редких случаях сохраняется в мозге, вызывая прогрессивное неврологическое расстройство, субакатное склерозирование панэнцефалита (SSPE). MeV имеет два конвертных гликпротеинов, гемагглютинина (H) и синтеза (F) белков. Белок H обладает доменом головы, который изначально служит посредником в связывании рецептора, и доменом стеблей, который затем передает импульсный сигнал синтеза на протеин F. Недавно мы показали, что молекула сцепления клеток 1 (CADM1; также из

Совпадение в аннотации оригинала
Measles virus (MeV), an enveloped RNA virus in the family Paramyxoviridae, usually causes acute febrile illness with skin rash but in rare c … SynCAM1) and CADM2 (also known as IGSF4D, Necl-3, and SynCAM2) are host factors enabling cell-cell membrane fusion mediated by hyperfusogenic F proteins of neuropathogenic MeVs as well as MeV spread between neurons lacking the known receptors. CADM1 and CADM2 interact in cis with the H protein on the same cell membrane, triggering hyperfusogenic F protein-mediat …

The lymphoma-associated fusion tyrosine kinase ITK-SYK requires pleckstrin homology domain-mediated membrane localization for activation and cellular transformation.

ITK-SYK, a novel fusion tyrosine kinase (FTK) resulting from a recurrent t(5;9)(q33;q22), was recently identified in a poorly understood subset of peripheral T-cell lymphomas. However, the biochemical and functional properties of ITK-SYK are unknown. Here we demonstrate that ITK-SYK is a catalytically active tyrosine kinase that is sensitive to an established inhibitor of SYK. The expression of ITK-SYK, but not SYK, transformed NIH3T3 cells, inducing loss of contact inhibition and formation of anchorage-independent colonies in soft agar, in a kinase activity-dependent manner. ITK-SYK is unusua

[Establishment and application of enzyme linked immunosorbent assay based on the outer membrane pIA-pIB fusion gene of Neisseria gonorrhoeae].

OBJECTIVE: To clone pIA and pIB genes of Neisseria gonorrhoeae,and to construct pIA-pIB fusion gene and its prokaryotic expression system, and to establish enzyme linked immunosorbent assay (ELISA) based on rPIA-PIB for detecting serum and pus samples from gonorrhea patients and to evaluate the sensitivity and specificity of the ELISA. METHODS: pIA-pIB fusion gene was constructed by polymerase chain reaction (PCR) using linking primers and a prokaryotic expression system of the fusion gene was constructed by using routine molecular biological methods. Sodium dodecyl sulfate-polyacrylamide gel

Antigen-Enriched Tumor-Dendritic Cell Fusion Membrane-Coated Metal-Phenolic Nanovaccine Enables Dual T-Cell Activation for Robust Cancer Immunotherapy.

Antigen-enriched tumor vaccines represent a promising strategy for cancer immunotherapy. Nevertheless, their clinical efficacy is often limited by insufficient antigen presentation and low immunogenicity. Here, a novel nanovaccine was developed that synergistically combines mitochondrial fission inhibition, tumor-dendritic cell fusion, and metal-phenolic nanoparticle technology. Tumor cells were pretreated with the mitochondrial fission inhibitor Mdivi‑1, yielding antigen‑enriched cell membranes (CM(M)). Subsequently, these CM(M) were fused with the dendritic cell membranes (DCM) overexpressin

Effective in Vivo Targeting of Influenza Virus through a Cell-Penetrating/Fusion Inhibitor Tandem Peptide Anchored to the Plasma Membrane.

The impact of influenza virus infection is felt each year on a global scale when approximately 5-10% of adults and 20-30% of children globally are infected. While vaccination is the primary strategy for influenza prevention, there are a number of likely scenarios for which vaccination is inadequate, making the development of effective antiviral agents of utmost importance. Anti-influenza treatments with innovative mechanisms of action are critical in the face of emerging viral resistance to the existing drugs. These new antiviral agents are urgently needed to address future epidemic (or pandem

Membrane anchoring of Epstein-Barr virus gp42 inhibits fusion with B cells even with increased flexibility allowed by engineered spacers.

UNLABELLED: We recently described the architecture of the Epstein-Barr virus (EBV) fusion-triggering complex consisting of the EBV B cell receptor human leukocyte antigen (HLA) class II and the EBV-encoded proteins gp42 and gH/gL. The architecture of this structure positioned the main body of gp42, comprising the C-type lectin domain (CTLD), away from the membrane and distant from where the membrane-bound form of gp42 might be tethered. gp42 is a type II membrane glycoprotein, with functional gp42 formed by cleavage near the gp42 amino-terminal transmembrane domain. This cleavage results in an

Peptide hormone release monitored from single vesicles in "membrane lawns" of differentiated male pituitary cells: SNAREs and fusion pore widening.

In this study we used live-cell immunocytochemistry and confocal microscopy to study the release from a single vesicle in a simplified system called membrane lawns. The lawns were prepared by exposing differentiated pituitary prolactin (PRL)-secreting cells to a hypoosmotic shear stress. The density of the immunolabeled ternary soluble N-ethylmaleimide-sensitive factor-attachment protein receptor (SNARE) complexes that bind complexin was approximately 10 times lower than the PRL-positive, lawn-resident vesicles; this indicates that some but not all vesicles are associated with ternary SNARE co

Induction of heterosubtypic cross-protection against influenza by a whole inactivated virus vaccine: the role of viral membrane fusion activity.

BACKGROUND: The inability of seasonal influenza vaccines to effectively protect against infection with antigenically drifted viruses or newl … ed for virus inactivation influence optimal activation of CTLs by WIV, most likely by affecting the membrane fusion properties of the virus. Specifically, inactivation with formalin (FA) severely compromises fusion activity of the virus, while inactivation with β-propiolactone (BPL) preserves fusion activity. Here, we demonstrate that vaccination of mice with BPL …

Survival of the fittest: positive selection of CD4+ T cells expressing a membrane-bound fusion inhibitor following HIV-1 infection.

Although a variety of genetic strategies have been developed to inhibit HIV replication, few direct comparisons of the efficacy of these inhibitors have been carried out. Moreover, most studies have not examined whether genetic inhibitors are able to induce a survival advantage that results in an expansion of genetically-modified cells following HIV infection. We evaluated the efficacy of three leading genetic strategies to inhibit HIV replication: 1) an HIV-1 tat/rev-specific small hairpin (sh) RNA; 2) an RNA antisense gene specific for the HIV-1 envelope; and 3) a viral entry inhibitor, maC4

SERINC5 co-expressed with HIV-1 Env or present in a target membrane destabilizes small fusion pores leading to their collapse.

Serine incorporator protein 5 (SERINC5) is a multipass membrane protein that reduces infectivity of retroviruses and other enveloped viruses through incorporating into budding virions and inhibiting their ability to fuse with target cells. Several mechanisms for anti-HIV activity of SERINC5 have been reported, including binding to Env glycoprotein, induction of conformational changes and destabilization of Env, as well as disruption of transmembrane asymmetry of viral envelope. All these reported anti-HIV mechanisms involve SERINC5 incorporation into progeny virions, while there is very little

pH Optimum of Hemagglutinin-Mediated Membrane Fusion Determines Sensitivity of Influenza A Viruses to the Interferon-Induced Antiviral State and IFITMs.

The replication and pathogenicity of influenza A viruses (IAVs) critically depend on their ability to tolerate the antiviral interferon (IFN … 1 and H7N9 viruses. In A549 and Calu-3 cells, viruses displaying a higher pH optimum of HA-mediated membrane fusion, H5N1-PR8 and H7N9-PR8, were less sensitive to the IFN-induced antiviral state than their counterparts with HAs from duck and human viruses, which fused at a lower pH. The association between a high pH optimum of fusion and reduced IFN sensitivity w …

EmrA1 membrane fusion protein of Francisella tularensis LVS is required for resistance to oxidative stress, intramacrophage survival and virulence in mice.

Francisella tularensis is a category A biodefence agent that causes a fatal human disease known as tularaemia. The pathogenicity of F. tularensis depends on its ability to persist inside host immune cells primarily by resisting an attack from host-generated reactive oxygen and nitrogen species (ROS/RNS). Based on the ability of F. tularensis to resist high ROS/RNS levels, we have hypothesized that additional unknown factors act in conjunction with known antioxidant defences to render ROS resistance. By screening a transposon insertion library of F. tularensis LVS in the presence of hydrogen pe

Vamp3/syntaxin 4 mediates the basolateral membrane fusion of TfR transcytosis across the BBB and is exploited by pathogenic E. coli.

Transcytosis across the blood-brain barrier (BBB), composed of brain microvascular endothelial cells (HBMECs), is tightly controlled to prevent the entry of macromolecules, microorganisms, and toxins into the brain. Transferrin receptor (TfR) transcytosis, one of the few active transcytosis pathways in HBMECs, is extensively utilized for drug transport across the BBB and employed by meningitis-causing bacteria to penetrate into the brain. However, the molecular mechanism facilitating the fusion of TfR vesicles with the basolateral membrane of HBMECs, the final step of transcytosis, has not bee

Small molecule inhibits respiratory syncytial virus entry and infection by blocking the interaction of the viral fusion protein with the cell membrane.

Antiviral drug development against respiratory syncytial virus (RSV) is urgently needed due to the public health significance of the viral infection. Here, we report the anti-RSV activity of a small molecule, (1S,3R,4R,5R)-3,4- bis{[(E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]oxy}-1,5-dihydroxycyclohexane-1-carboxylic methyl ester (3,4-DCQAME) or 3,4- O-Dicaffeoylquinic acid methyl ester, which can be isolated from several plants of traditional Chinese medicine. We showed for the first time that compound 3,4-DCQAME potently inhibits RSV entry and infection. In vitro, 3,4-DCQAME can interact with F

Using Disposable Membrane Cell Collector to Enrich Lung Adenocarcinoma Cells in Bloody Pleural Effusion for Anaplastic Lymphoma Kinase Fusion Gene Detection.

PURPOSE: For anaplastic lymphoma kinase (ALK) gene detection, the centrifugal sedimentation method (CSM) and cell block method (CBM) are commonly used to process samples of bloody pleural effusions (BPEs). However, in practice, the impurity content in the processed samples often affects the results and even leads to the detection failure. The purpose of this study was to establish a cell enrichment method (CEM) by using a disposable membrane cell collector to remove blood and inflammatory cells and enrich lung adenocarcinoma cells in BPE for more efficient RNA extraction and ALK gene detection

Mechanistic insights of host cell fusion of SARS-CoV-1 and SARS-CoV-2 from atomic resolution structure and membrane dynamics.

The emerging and re-emerging viral diseases are continuous threats to the wellbeing of human life. Previous outbreaks of Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS had evidenced potential threats of coronaviruses in human health. The recent pandemic due to SARS-CoV-2 is overwhelming and has been going beyond control. Vaccines and antiviral drugs are ungently required to mitigate the pandemic. Therefore, it is important to comprehend the mechanistic details of viral infection process. The fusion between host cell and virus being the first step of infecti

Membrane-Anchored and Sequence-Oriented Antiviral Activity of Fusion-Inhibitory Lipopeptides Derived from the SARS-CoV-2 Spike Glycoprotein S2 Subunit.

BACKGROUND: SARS-CoV-2 fusion inhibitory peptides represent promising antiviral candidates. Recently, a 19-mer peptide (PN19)-designed in our laboratory to mimic the internal fusion peptide of the SARS-CoV-2 spike S2 subunit-demonstrated potent antiviral activity and stable conformational features. OBJECTIVES: To investigate how this antiviral activity depends on membrane interactions, we designed synthetic PN19 lipopeptide derivatives and evaluated their efficacy against SARS-CoV-2 replication. METHODS: Lipopeptides were synthesized by conjugating cholesterol to either the N- or C-terminus

The F1148 hydrophobic lock: A critical determinant of SARS-CoV-2 spike protein-mediated membrane fusion via the 3H/CH cavity.

The S2 subunit of the coronavirus Spike protein undergoes extensive conformational refolding to drive membrane fusion during viral entry. Although the HR1/HR2 six-helix bundle (6-HB) is recognized as the core mediator of fusion, the molecular driving force governing its formation remains poorly elucidated. Here, through systematic mutagenesis of the AlphaFold-predicted stem helix (SH) region in S2, followed by analysis of the resulting SC2-VLP entry phenotypes, we identified key amino acid residues within conserved helices that are present in both prefusion and postfusion Spike conformations. …

Laser Powder Bed Fusion (LPBF) WE43 Magnesium Scaffold with EGCG/PDA-Functionalized Silk Fibroin Membrane for Antibacterial Osteoinductive Guided Bone Regeneration.

Guided bone regeneration (GBR) is a prominent focus in biomedical materials research, yet few studies address practical clinical needs. GBR membranes must fulfill the "PASS" principles to be effective in surgery, but existing membranes often fall short in balancing antibacterial activity, controlled degradation, osteoinductive potential, and mechanical support. In this study, we employed laser powder bed fusion (LPBF) to fabricate a porous WE43 magnesium alloy scaffold suitable for large alveolar bone defects. We then used electrospinning and layer-by-layer (LBL) self-assembly to create a silk