scholarly journals Viral Membrane Fusion Proteins and RNA Sorting Mechanisms for the Molecular Delivery by Exosomes

2021 ◽  
Author(s):  
Ilya Zubarev ◽  
Dmitry Vladimirtsev ◽  
Maria Vorontsova ◽  
Igor Blatov ◽  
Konstantin Shevchenko ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Extracellular Vesicles ◽  
Targeted Delivery ◽  
Fusion Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Viral Fusion ◽  
Viral Membrane ◽  
Membrane Fusion Proteins ◽  
Viral Membrane Fusion

The advancement of precision medicine critically depends on the robustness and specificity of the carriers used for the targeted delivery of effector molecules in the human body. Numerous nanocarriers have been explored in vivo, to ensure the precise delivery of molecular cargos via tissue-specific targeting, including the endocrine part of the pancreas, thyroid, and adrenal glands. However, even after reaching the target organ, the cargo-carrying vehicle needs to enter the cell and then escape from lysosomal destruction. Most of artificial nanocarriers suffer from intrinsic limitations that either prevent them from completing the specific delivery of the cargo. In this respect, extracellular vesicles (EVs) seem to be the natural tool for payload delivery due to their versatility and low toxicity. However, EV-mediated delivery is not selective and usually short-ranged. By inserting the viral membrane fusion proteins into exosomes, it is possible to increase the efficiency of membrane recognition and also ease the process of membrane fusion. This review describes the molecular details of the viral-assisted interaction between the target cell and extracellular vesicles. We also discuss the question of the usability of viral fusion proteins in developing extracellular vesicle-based nanocarriers with higher efficacy of payload delivery. Finally, this review specifically highlights the role of Gag and RNA binding proteins in RNA sorting into extracellular vesicles.

scholarly journals Viral Membrane Fusion Proteins and RNA Sorting Mechanisms for the Molecular Delivery by Exosomes

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3043
Author(s):  
Ilya Zubarev ◽  
Dmitry Vladimirtsev ◽  
Maria Vorontsova ◽  
Igor Blatov ◽  
Konstantin Shevchenko ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Targeted Delivery ◽  
Fusion Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Viral Fusion ◽  
Viral Membrane ◽  
Membrane Fusion Proteins ◽  
Viral Membrane Fusion

The advancement of precision medicine critically depends on the robustness and specificity of the carriers used for the targeted delivery of effector molecules in the human body. Numerous nanocarriers have been explored in vivo, to ensure the precise delivery of molecular cargos via tissue-specific targeting, including the endocrine part of the pancreas, thyroid, and adrenal glands. However, even after reaching the target organ, the cargo-carrying vehicle needs to enter the cell and then escape lysosomal destruction. Most artificial nanocarriers suffer from intrinsic limitations that prevent them from completing the specific delivery of the cargo. In this respect, extracellular vesicles (EVs) seem to be the natural tool for payload delivery due to their versatility and low toxicity. However, EV-mediated delivery is not selective and is usually short-ranged. By inserting the viral membrane fusion proteins into exosomes, it is possible to increase the efficiency of membrane recognition and also ease the process of membrane fusion. This review describes the molecular details of the viral-assisted interaction between the target cell and EVs. We also discuss the question of the usability of viral fusion proteins in developing extracellular vesicle-based nanocarriers with a higher efficacy of payload delivery. Finally, this review specifically highlights the role of Gag and RNA binding proteins in RNA sorting into EVs.

scholarly journals Class III viral membrane fusion proteins

2009 ◽  
Vol 19 (2) ◽  
pp. 189-196 ◽  
Author(s):  
Marija Backovic ◽  
Theodore S Jardetzky
Keyword(s):  
Membrane Fusion ◽  
Fusion Proteins ◽  
Class Iii ◽  
Viral Membrane ◽  
Membrane Fusion Proteins ◽  
Viral Membrane Fusion

scholarly journals Structures and Mechanisms of Viral Membrane Fusion Proteins: Multiple Variations on a Common Theme

2008 ◽  
Vol 43 (3) ◽  
pp. 189-219 ◽  
Author(s):  
Judith M. White ◽  
Sue E. Delos ◽  
Matthew Brecher ◽  
Kathryn Schornberg
Keyword(s):  
Membrane Fusion ◽  
Fusion Proteins ◽  
Common Theme ◽  
Viral Membrane ◽  
Membrane Fusion Proteins ◽  
Viral Membrane Fusion

scholarly journals Fusogenic Reoviruses and Their Fusion-Associated Small Transmembrane (FAST) Proteins

2019 ◽  
Vol 6 (1) ◽  
pp. 341-363 ◽  
Author(s):  
Roy Duncan
Keyword(s):  
Membrane Fusion ◽  
Fusion Proteins ◽  
Syncytium Formation ◽  
Nonstructural Proteins ◽  
Enveloped Virus ◽  
Fast Proteins ◽  
Nonenveloped Virus ◽  
Functional Features ◽  
Membrane Fusion Proteins ◽  
Viral Membrane Fusion

With no limiting membrane surrounding virions, nonenveloped viruses have no need for membrane fusion to gain access to intracellular replication compartments. Consequently, nonenveloped viruses do not encode membrane fusion proteins. The only exception to this dogma is the fusogenic reoviruses that encode fusion-associated small transmembrane (FAST) proteins that induce syncytium formation. FAST proteins are the smallest viral membrane fusion proteins and, unlike their enveloped virus counterparts, are nonstructural proteins that evolved specifically to induce cell-to-cell, not virus-cell, membrane fusion. This distinct evolutionary imperative is reflected in structural and functional features that distinguish this singular family of viral fusogens from all other protein fusogens. These rudimentary fusogens comprise specific combinations of different membrane effector motifs assembled into small, modular membrane fusogens. FAST proteins offer a minimalist model to better understand the ubiquitous process of protein-mediated membrane fusion and to reveal novel mechanisms of nonenveloped virus dissemination that contribute to virulence.

scholarly journals Localization and Regulation of the T1 Unimolecular Spanin

2018 ◽  
Vol 92 (22) ◽  
Author(s):  
Rohit Kongari ◽  
Jeffrey Snowden ◽  
Joel D. Berry ◽  
Ry Young
Keyword(s):  
Membrane Fusion ◽  
Outer Membrane ◽  
Fusion Proteins ◽  
Transmembrane Domain ◽  
Time Lapse ◽  
Negative Regulator ◽  
Viral Fusion ◽  
Outer Membranes ◽  
Two Component ◽  
Membrane Fusion Proteins

ABSTRACTSpanins are bacteriophage lysis proteins responsible for disruption of the outer membrane, the final step of Gram-negative host lysis. The absence of spanins results in a terminal phenotype of fragile spherical cells. The phage T1 employs a unimolecular spanin gp11that has an N-terminal lipoylation signal and a C-terminal transmembrane domain. Upon maturation and localization, gp11ends up as an outer membrane lipoprotein with a C-terminal transmembrane domain embedded in the inner membrane, thus connecting both membranes as a covalent polypeptide chain. Unlike the two-component spanins encoded by most of the other phages, including lambda, the unimolecular spanins have not been studied extensively. In this work, we show that the gp11mutants lacking either membrane localization signal were nonfunctional and conferred a partially dominant phenotype. Translation from internal start sites within the gp11coding sequence generated a shorter product which exhibited a negative regulatory effect on gp11function. Fluorescence spectroscopy time-lapse videos of gp11-GFP expression showed gp11accumulated in distinct punctate foci, suggesting localized clusters assembled within the peptidoglycan meshwork. In addition, gp11was shown to mediate lysis in the absence of holin and endolysin function when peptidoglycan density was depleted by starvation for murein precursors. This result indicates that the peptidoglycan is a negative regulator of gp11function. This supports a model in which gp11acts by fusing the inner and outer membranes, a mode of action analogous to but mechanistically distinct from that proposed for the two-component spanin systems.IMPORTANCESpanins have been proposed to fuse the cytoplasmic and outer membranes during phage lysis. Recent work with the lambda spanins Rz-Rz1, which are similar to class I viral fusion proteins, has shed light on the functional domains and requirements for two-component spanin function. Here we report, for the first time, a genetic and biochemical approach to characterize unimolecular spanins, which are structurally and mechanistically different from two-component spanins. Considering similar predicted secondary structures within the ectodomains, unimolecular spanins can be regarded as a prokaryotic version of type II viral membrane fusion proteins. This study not only adds to our understanding of regulation of phage lysis at various levels but also provides a prokaryotic genetically tractable platform for interrogating class II-like membrane fusion proteins.

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