Extracellular Vesicles in Viral Infections of the Nervous System

Kutchy, Naseer A.; Peeples, Eric S.; Sil, Susmita; Liao, Ke; Chivero, Ernest T.; Hu, Guoku; Buch, Shilpa

doi:10.3390/v12070700

Cited by 28 publications

(18 citation statements)

References 200 publications

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“…Moreover, additional brain diseases are due to genetic defects such as those of miRNAs [131]. In all these [130][131][132][133] and other additional diseases, EVs play key roles analogous to those described in the present review. For most brain diseases, functional mechanisms are known.…”

Section: Discussionsupporting

confidence: 52%

“…At present, the EVs, tools for the introduction of innovative processes, are important especially for brain diseases such as the immunological and neurodegenerative diseases. It should be mentioned, however, that other important brain diseases exist, including traumatic brain and spinal cord injuries, stroke, epilepsy, viral diseases, cancer (gliomas) [130][131][132]. Moreover, additional brain diseases are due to genetic defects such as those of miRNAs [131].…”

Section: Discussionmentioning

confidence: 99%

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Extracellular vesicles (exosomes and ectosomes) play key roles in the pathology of brain diseases

Meldolesi

2021

Mol Biomed

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Last century, neurons and glial cells were mostly believed to play distinct functions, relevant for the brain. Progressively, however, it became clear that neurons, astrocytes and microglia co-operate intensely with each other by release/binding of signaling factors, direct surface binding and generation/release of extracellular vesicles, the exosomes and ectosomes, called together vesicles in this abstract. The present review is focused on these vesicles, fundamental in various brain diseases. Their properties are extraordinary. The specificity of their membrane governs their fusion with distinct target cells, variable depending on the state and specificity of their cells of origin and target. Result of vesicle fusion is the discharge of their cargos into the cytoplasm of target cells. Cargos are composed of critical molecules, from proteins (various nature and function) to nucleotides (especially miRNAs), playing critical roles in immune and neurodegenerative diseases. Among immune diseases is multiple sclerosis, affected by extensive dysregulation of co-trafficking neural and glial vesicles, with distinct miRNAs inducing severe or reducing effects. The vesicle-dependent differences between progressive and relapsing-remitting forms of the disease are relevant for clinical developments. In Alzheimer’s disease the vesicles can affect the brain by changing their generation and inducing co-release of effective proteins, such Aβ and tau, from neurons and astrocytes. Specific miRNAs can delay the long-term development of the disease. Upon their traffic through the blood-brainbarrier, vesicles of various origin reach fluids where they are essential for the identification of biomarkers, important for diagnostic and therapeutic innovations, critical for the future of many brain patients.

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Section: Discussionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Extracellular vesicles (exosomes and ectosomes) play key roles in the pathology of brain diseases

Meldolesi

2021

Mol Biomed

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“…Exosomes released from virus-infected cells are associated with a viral infection, host immunity, and microenvironmental modulation [ 11 ]. Exosomes secreted by enveloped viruses, such as HIV, hepatitis C virus (HCV), and human lymphotropic virus (HTLV), are attracting increasing attention [ 33 , 85 , 86 ].…”

Section: Roles Of Exosomes In the Transmission And Replication Of mentioning

confidence: 99%

Recent Progress on Exosomes in RNA Virus Infection

Zhang

Chen

et al. 2021

Viruses

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Recent research indicates that most tissue and cell types can secrete and release membrane-enclosed small vesicles, known as exosomes, whose content reflects the physiological/pathological state of the cells from which they originate. These exosomes participate in the communication and cell-to-cell transfer of biologically active proteins, lipids, and nucleic acids. Studies of RNA viruses have demonstrated that exosomes release regulatory factors from infected cells and deliver other functional host genetic elements to neighboring cells, and these functions are involved in the infection process and modulate the cellular responses. This review provides an overview of the biogenesis, composition, and some of the most striking functions of exosome secretion and identifies physiological/pathological areas in need of further research. While initial indications suggest that exosome-mediated pathways operate in vivo, the exosome mechanisms involved in the related effects still need to be clarified. The current review focuses on the role of exosomes in RNA virus infections, with an emphasis on the potential contributions of exosomes to pathogenesis.

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“…The role of EV in SARS-CoV-2 infection has been reviewed recently by Hassanpour et al [ 56 ] on the basis of their contribution to spread the virus, based on their role in transporting receptors as CD9 and ACE2, which make recipient cells susceptible to virus docking. It is also worth mentioning that EVs play important roles in the viral spread and replication [ 57 , 58 ], particularly of HIV, HCV and SARS [ 59 ], Newcastle disease virus [ 60 ], HPV [ 61 ], flavivirus infection [ 62 ], as well as in the pathogenicity of certain viruses in the nervous system [ 63 ].…”

Section: Resultsmentioning

confidence: 99%

Protein-Driven Mechanism of Multiorgan Damage in COVID-19

Estrada¹

2020

Medicine in Drug Discovery

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We propose a new plausible mechanism by mean of which SARS-CoV-2 produces extrapulmonary damages in severe COVID-19 patients. The mechanism consist on the existence of vulnerable proteins (VPs), which are (i) mainly expressed outside the lungs; (ii) their perturbations is known to produce human diseases; and (iii) can be perturbed directly or indirectly by SARS-CoV-2 proteins. These VPs are perturbed by other proteins, which are: (i) mainly expressed in the lungs, (ii) are targeted directly by SARS-CoV-2 proteins, (iii) can navigate outside the lungs as cargo of extracellular vesicles (EVs); and (iv) can activate VPs via subdiffusive processes inside the target organ. Using bioinformatic tools and mathematical modeling we identifies 26 VPs and their 38 perturbators, which predict extracellular damages in the immunologic endocrine, cardiovascular, circulatory, lymphatic, musculoskeletal, neurologic, dermatologic, hepatic, gastrointestinal, and metabolic systems, as well as in the eyes. The identification of these VPs and their perturbators allow us to identify 27 existing drugs which are candidates to be repurposed for treating extrapulmonary damage in severe COVID-19 patients. After removal of drugs having undesirable drug-drug interactions we select 7 drugs and one natural product: apabetalone, romidepsin, silmitasertib, ozanezumab, procaine, azacitidine, amlexanox, volociximab, and ellagic acid, whose combinations can palliate the organs and systems found to be damaged by COVID-19. We found that at least 4 drugs are needed to treat all the multiorgan damages, for instance: the combination of romidepsin, silmitasertib, apabetalone and azacitidine.

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Extracellular Vesicles in Viral Infections of the Nervous System

Cited by 28 publications

References 200 publications

Extracellular vesicles (exosomes and ectosomes) play key roles in the pathology of brain diseases

Extracellular vesicles (exosomes and ectosomes) play key roles in the pathology of brain diseases

Recent Progress on Exosomes in RNA Virus Infection

Protein-Driven Mechanism of Multiorgan Damage in COVID-19

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