scholarly journals Extracellular Vesicles in Viral Replication and Pathogenesis and Their Potential Role in Therapeutic Intervention

Viruses ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 887 ◽  
Author(s):  
Asit Kumar ◽  
Sunitha Kodidela ◽  
Erene Tadrous ◽  
Theodore James Cory ◽  
Crystal Martin Walker ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Plasma Membrane ◽  
Extracellular Vesicles ◽  
Cellular Response ◽  
Viral Infections ◽  
Genetic Material ◽  
Virus Propagation ◽  
Therapeutic Implications ◽  
Antiretroviral Drug ◽  
Infected Cells

Extracellular vesicles (EVs) have shown their potential as a carrier of molecular information, and they have been involved in physiological functions and diseases caused by viral infections. Virus-infected cells secrete various lipid-bound vesicles, including endosome pathway-derived exosomes and microvesicles/microparticles that are released from the plasma membrane. They are released via a direct outward budding and fission of plasma membrane blebs into the extracellular space to either facilitate virus propagation or regulate the immune responses. Moreover, EVs generated by virus-infected cells can incorporate virulence factors including viral protein and viral genetic material, and thus can resemble noninfectious viruses. Interactions of EVs with recipient cells have been shown to activate signaling pathways that may contribute to a sustained cellular response towards viral infections. EVs, by utilizing a complex set of cargos, can play a regulatory role in viral infection, both by facilitating and suppressing the infection. EV-based antiviral and antiretroviral drug delivery approaches provide an opportunity for targeted drug delivery. In this review, we summarize the literature on EVs, their associated involvement in transmission in viral infections, and potential therapeutic implications.

scholarly journals Extracellular Vesicles in Viral Infections: Two Sides of the Same Coin?

2020 ◽  
Vol 10 ◽  
Author(s):  
Sharon de Toledo Martins ◽  
Lysangela Ronalte Alves
Keyword(s):  
Extracellular Vesicles ◽  
Viral Infections ◽  
Complex Function ◽  
Molecular Signature ◽  
Membrane Structures ◽  
Viral Genomes ◽  
Antiviral Responses ◽  
Diagnostic Approaches ◽  
Infected Cells ◽  
Emerging Viral Diseases

Extracellular vesicles are small membrane structures containing proteins and nucleic acids that are gaining a lot of attention lately. They are produced by most cells and can be detected in several body fluids, having a huge potential in therapeutic and diagnostic approaches. EVs produced by infected cells usually have a molecular signature that is very distinct from healthy cells. For intracellular pathogens like viruses, EVs can have an even more complex function, since the viral biogenesis pathway can overlap with EV pathways in several ways, generating a continuum of particles, like naked virions, EVs containing infective viral genomes and quasi-enveloped viruses, besides the classical complete viral particles that are secreted to the extracellular space. Those particles can act in recipient cells in different ways. Besides being directly infective, they also can prime neighbor cells rendering them more susceptible to infection, block antiviral responses and deliver isolated viral molecules. On the other hand, they can trigger antiviral responses and cytokine secretion even in uninfected cells near the infection site, helping to fight the infection and protect other cells from the virus. This protective response can also backfire, when a massive inflammation facilitated by those EVs can be responsible for bad clinical outcomes. EVs can help or harm the antiviral response, and sometimes both mechanisms are observed in infections by the same virus. Since those pathways are intrinsically interlinked, understand the role of EVs during viral infections is crucial to comprehend viral mechanisms and respond better to emerging viral diseases.

scholarly journals Extracellular vesicles and viruses: Are they close relatives?

2016 ◽  
Vol 113 (33) ◽  
pp. 9155-9161 ◽  
Author(s):  
Esther Nolte-‘t Hoen ◽  
Tom Cremer ◽  
Robert C. Gallo ◽  
Leonid B. Margolis
Keyword(s):  
Viral Infection ◽  
Extracellular Vesicles ◽  
Targeted Drug Delivery ◽  
Genetic Material ◽  
Cell Communication ◽  
Viral Proteins ◽  
Phospholipid Membrane ◽  
Infected Cells ◽  
Close Relatives ◽  
Physical And Chemical

Extracellular vesicles (EVs) released by various cells are small phospholipid membrane-enclosed entities that can carry miRNA. They are now central to research in many fields of biology because they seem to constitute a new system of cell–cell communication. Physical and chemical characteristics of many EVs, as well as their biogenesis pathways, resemble those of retroviruses. Moreover, EVs generated by virus-infected cells can incorporate viral proteins and fragments of viral RNA, being thus indistinguishable from defective (noninfectious) retroviruses. EVs, depending on the proteins and genetic material incorporated in them, play a significant role in viral infection, both facilitating and suppressing it. Deciphering the mechanisms of EV-cell interactions may facilitate the design of EVs that inhibit viral infection and can be used as vehicles for targeted drug delivery.

scholarly journals Delivery of microRNAs by Extracellular Vesicles in Viral Infections: Could the News be Packaged?

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 611 ◽  
Author(s):  
Fabio Seiti Yamada Yoshikawa ◽  
Franciane Mouradian Emidio Teixeira ◽  
Maria Notomi Sato ◽  
Luanda Mara da Silva Oliveira
Keyword(s):  
Extracellular Vesicles ◽  
Viral Infections ◽  
Cell Communication ◽  
Donor Cell ◽  
Target Cells ◽  
Immune Recognition ◽  
Messenger Rnas ◽  
Pathological Conditions ◽  
Infected Cells ◽  
Cell Profile

Extracellular vesicles (EVs) are released by various cells and recently have attracted attention because they constitute a refined system of cell–cell communication. EVs deliver a diverse array of biomolecules including messenger RNAs (mRNAs), microRNAs (miRNAs), proteins and lipids, and they can be used as potential biomarkers in normal and pathological conditions. The cargo of EVs is a snapshot of the donor cell profile; thus, in viral infections, EVs produced by infected cells could be a central player in disease pathogenesis. In this context, miRNAs incorporated into EVs can affect the immune recognition of viruses and promote or restrict their replication in target cells. In this review, we provide an updated overview of the roles played by EV-delivered miRNAs in viral infections and discuss the potential consequences for the host response. The full understanding of the functions of EVs and miRNAs can turn into useful biomarkers for infection detection and monitoring and/or uncover potential therapeutic targets.

scholarly journals Chitosan-Based Nanoparticles Against Viral Infections

2021 ◽  
Vol 11 ◽  
Author(s):  
Homa Boroumand ◽  
Fereshteh Badie ◽  
Samaneh Mazaheri ◽  
Zeynab Sadat Seyedi ◽  
Javid Sadri Nahand ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Viral Infections ◽  
Therapeutic Potential ◽  
Host Cells ◽  
Host Immune System ◽  
Naturally Occurring ◽  
The Us ◽  
Infected Cells ◽  
Therapeutic Tools

Viral infections, in addition to damaging host cells, can compromise the host immune system, leading to frequent relapse or long-term persistence. Viruses have the capacity to destroy the host cell while liberating their own RNA or DNA in order to replicate within additional host cells. The viral life cycle makes it challenging to develop anti-viral drugs. Nanotechnology-based approaches have been suggested to deal effectively with viral diseases, and overcome some limitations of anti-viral drugs. Nanotechnology has enabled scientists to overcome the challenges of solubility and toxicity of anti-viral drugs, and can enhance their selectivity towards viruses and virally infected cells, while preserving healthy host cells. Chitosan is a naturally occurring polymer that has been used to construct nanoparticles (NPs), which are biocompatible, biodegradable, less toxic, easy to prepare, and can function as effective drug delivery systems (DDSs). Furthermore, chitosan is Generally Recognized as Safe (GRAS) by the US Food and Drug Administration (U.S. FDA). Chitosan NPs have been used in drug delivery by the oral, ocular, pulmonary, nasal, mucosal, buccal, or vaginal routes. They have also been studied for gene delivery, vaccine delivery, and advanced cancer therapy. Multiple lines of evidence suggest that chitosan NPs could be used as new therapeutic tools against viral infections. In this review we summarize reports concerning the therapeutic potential of chitosan NPs against various viral infections.

scholarly journals Mechanistic and Therapeutic Implications of Extracellular Vesicles as a Potential Link Between Covid-19 and Cardiovascular Disease Manifestations

2021 ◽  
Vol 9 ◽  
Author(s):  
Gianluigi Pironti ◽  
Daniel C. Andersson ◽  
Lars H. Lund
Keyword(s):  
Extracellular Vesicles ◽  
Secretory Pathway ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Therapeutic Implications ◽  
Extracellular Signaling ◽  
Organ Manifestations ◽  
Potential Link ◽  
Infected Cells ◽  
Virus Spreading

Extracellular vesicles (EVs), which are cell released double layered membrane particles, have been found in every circulating body fluid, and provide a tool for conveying diverse information between cells, influencing both physiological and pathological conditions. Viruses can hijack the EVs secretory pathway to exit infected cells and use EVs endocytic routes to enter uninfected cells, suggesting that EVs and viruses can share common cell entry and biogenesis mechanisms. SARS-CoV-2 is responsible of the coronavirus disease 2019 (Covid-19), which may be accompanied by severe multi-organ manifestations. EVs may contribute to virus spreading via transfer of virus docking receptors such as CD9 and ACE2. Covid-19 is known to affect the renin angiotensin system (RAS), and could promote secretion of harmful EVs. In this scenario EVs might be linked to cardiovascular manifestations of the Covid-19 disease through unbalance in RAS. In contrast EVs derived from mesenchymal stem cells or cardiosphere derived cells, may promote cardiovascular function due to their beneficial effect on angiogenesis, fibrosis, contractility and immuno-modulation. In this article we assessed the potential impact of EVs in cardiovascular manifestations of Covid-19 and highlight potential strategies to control the extracellular signaling for future therapies.

scholarly journals Extracellular Vesicles: Roles in Human Viral Infections, Immune-Diagnostic, and Therapeutic Applications

Pathogens ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1056
Author(s):  
Ayodeji O. Ipinmoroti ◽  
Qiana L. Matthews
Keyword(s):  
Viral Infection ◽  
Extracellular Vesicles ◽  
Biomarker Discovery ◽  
Viral Infections ◽  
Human Adenovirus ◽  
Human Immune Deficiency Virus ◽  
Physiological Processes ◽  
Infection Diagnostics ◽  
Infected Cells ◽  
Intercellular Spread

Membrane-bound vesicles that are released from cells are increasingly being studied as a medium of intercellular communication, as these act to shuttle functional proteins, such as lipids, DNA, rRNA, and miRNA, between cells during essential physiological processes. Extracellular vesicles (EVs), most commonly exosomes, are consistently produced by virus-infected cells, and they play crucial roles in mediating communication between infected and uninfected cells. Notably, pathophysiological roles for EVs have been established in various viral infections, including human immune deficiency virus (HIV), coronavirus (CoV), and human adenovirus (HAdv). Retroviruses, such as HIV, modulate the production and composition of EVs, and critically, these viruses can exploit EV formation, secretion, and release pathways to promote infection, transmission, and intercellular spread. Consequently, EV production has been investigated as a potential tool for the development of improved viral infection diagnostics and therapeutics. This review will summarize our present knowledge of EV–virus relationships, focusing on their known roles in pathophysiological pathways, immunomodulatory mechanisms, and utility for biomarker discovery. This review will also discuss the potential for EVs to be exploited as diagnostic and treatment tools for viral infection.

scholarly journals ViralLink: An integrated workflow to investigate the effect of SARS-CoV-2 on intracellular signalling and regulatory pathways

2021 ◽  
Vol 17 (2) ◽  
pp. e1008685
Author(s):  
Agatha Treveil ◽  
Balazs Bohar ◽  
Padhmanand Sudhakar ◽  
Lejla Gul ◽  
Luca Csabai ◽  
...  
Keyword(s):  
Cellular Response ◽  
Viral Infections ◽  
A Priori ◽  
Interdisciplinary Approach ◽  
Intracellular Signalling ◽  
Regulatory Pathways ◽  
Tracheal Epithelial Cells ◽  
Infected Cells ◽  
Set Up ◽  
Context Specific

The SARS-CoV-2 pandemic of 2020 has mobilised scientists around the globe to research all aspects of the coronavirus virus and its infection. For fruitful and rapid investigation of viral pathomechanisms, a collaborative and interdisciplinary approach is required. Therefore, we have developed ViralLink: a systems biology workflow which reconstructs and analyses networks representing the effect of viruses on intracellular signalling. These networks trace the flow of signal from intracellular viral proteins through their human binding proteins and downstream signalling pathways, ending with transcription factors regulating genes differentially expressed upon viral exposure. In this way, the workflow provides a mechanistic insight from previously identified knowledge of virally infected cells. By default, the workflow is set up to analyse the intracellular effects of SARS-CoV-2, requiring only transcriptomics counts data as input from the user: thus, encouraging and enabling rapid multidisciplinary research. However, the wide-ranging applicability and modularity of the workflow facilitates customisation of viral context, a priori interactions and analysis methods. Through a case study of SARS-CoV-2 infected bronchial/tracheal epithelial cells, we evidence the functionality of the workflow and its ability to identify key pathways and proteins in the cellular response to infection. The application of ViralLink to different viral infections in a context specific manner using different available transcriptomics datasets will uncover key mechanisms in viral pathogenesis.

Caveolin-1, galectin-3 and lipid raft domains in cancer cell signalling

2015 ◽  
Vol 57 ◽  
pp. 189-201 ◽  
Author(s):  
Jay Shankar ◽  
Cecile Boscher ◽  
Ivan R. Nabi
Keyword(s):  
Plasma Membrane ◽  
Lipid Rafts ◽  
Cancer Cell ◽  
Cellular Response ◽  
Spatial Organization ◽  
Essential Feature ◽  
Cell Signalling ◽  
Coated Pits ◽  
Signalling Molecules ◽  
Raft Domains

Spatial organization of the plasma membrane is an essential feature of the cellular response to external stimuli. Receptor organization at the cell surface mediates transmission of extracellular stimuli to intracellular signalling molecules and effectors that impact various cellular processes including cell differentiation, metabolism, growth, migration and apoptosis. Membrane domains include morphologically distinct plasma membrane invaginations such as clathrin-coated pits and caveolae, but also less well-defined domains such as lipid rafts and the galectin lattice. In the present chapter, we will discuss interaction between caveolae, lipid rafts and the galectin lattice in the control of cancer cell signalling.

Exploring siRNA Umpired Nanogels: A Tale of Barrier Combating Carrier

2020 ◽  
Vol 26 (27) ◽  
pp. 3234-3250
Author(s):  
Sushil K. Kashaw ◽  
Prashant Sahu ◽  
Vaibhav Rajoriya ◽  
Pradeep Jana ◽  
Varsha Kashaw ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Biomedical Engineering ◽  
Viral Infections ◽  
Slow Release ◽  
Molecular Level ◽  
Release Kinetics ◽  
Biologically Active ◽  
Release Process ◽  
Rapid Release ◽  
Wide Range

Potential short interfering RNAs (siRNA) modulating gene expression have emerged as a novel therapeutic arsenal against a wide range of maladies and disorders containing cancer, viral infections, bacterial ailments and metabolic snags at the molecular level. Nanogel, in the current medicinal era, displayed a comprehensive range of significant drug delivery prospects. Biodegradation, swelling and de-swelling tendency, pHsensitive drug release and thermo-sensitivity are some of the renowned associated benefits of nanogel drug delivery system. Global researches have also showed that nanogel system significantly targets and delivers the biomolecules including DNAs, siRNA, protein, peptides and other biologically active molecules. Biomolecules delivery via nanogel system explored a wide range of pharmaceutical, biomedical engineering and agro-medicinal application. The siRNAs and DNAs delivery plays a vivacious role by addressing the hitches allied with chronic and contemporary therapeutic like generic possession and low constancy. They also incite release kinetics approach from slow-release while mingling to rapid release at the targets will be beneficial as interference RNAs delivery carriers. Therefore, in this research, we focused on the latest improvements in the delivery of siRNA loaded nanogels by enhancing the absorption, stability, sensitivity and combating the hindrances in cellular trafficking and release process.

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