Extracellular Vesicles and Viruses: Two Intertwined Entities

Moulin, Coline; Crupi, Mathieu J.F.; Ilkow, Carolina S.; Bell, John C.; Boulton, Stephen

doi:10.3390/ijms24021036

Cited by 35 publications

(21 citation statements)

References 174 publications

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“…Transmission at low MOI likely occurred through secondary infections, as uninfected cells remained available after the first round of infection. Additionally, transmission could be facilitated by collective viral infection (Maeda et al 1999; Cuevas, Durán-Moreno and Sanjuán 2017; Andreu-Moreno and Sanjuán 2018; Rosell et al 2021; Zavan et al 2023) or cell fusion (Buchrieser et al 2020; Leroy et al 2020; Rajah et al 2022; Zavan et al 2023). Under these conditions, a DVG could co-infect with a helper virus and be trans -complemented for successful propagation, even at an initially low MOI, despite of foundational effects could be more accused at low MOI and in some of the lineages the viral load got undetectable.…”

Section: Discussionmentioning

confidence: 99%

Accumulation dynamics of defective genomes during experimental evolution of two betacoronaviruses

Hillung,

Olmo-Uceda,

Muñoz-Sánchez

et al. 2024

Preprint

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Virus-encoded replicases often generate aberrant RNA genomes, known as defective viral genomes (DVGs). When coinfected with a helper virus providing necessary proteins, DVGs can multiply and spread. While DVGs depend on the helper virus for propagation, they can disrupt infectious virus replication, impact immune responses, and affect viral persistence or evolution. Understanding the dynamics of DVGs alongside standard viral genomes during infection remains unclear. To address this, we conducted a long-term experimental evolution of two betacoronaviruses, the human coronavirus OC43 (HCoV-OC43) and the murine hepatitis virus (MHV), in cell culture at both high and low multiplicities of infection (MOI). We then performed RNA-seq at regular time intervals, reconstructed DVGs, and analyzed their accumulation dynamics. Our findings indicate that DVGs evolved to exhibit greater diversity and abundance, with deletions and insertions being the most common types. Notably, some high MOI deletions showed very limited temporary existence, while others became prevalent over time. We observed differences in DVG abundance between high and low MOI conditions in HCoV-OC43 samples. The size distribution of HCoV-OC43 genomes with deletions differed between high and low MOI passages. In low MOI lineages, short and long DVGs were most common, with an additional cluster in high MOI lineages which became more prevalent along evolutionary time. MHV also showed variations in DVG size distribution at different MOI conditions, though less pronounced compared to HCoV-OC43, suggesting a more random distribution of DVG sizes. We identified hotspot regions for deletions that evolved at high MOI, primarily within cistrons encoding structural and accessory proteins. In conclusion, our study illustrates the widespread formation of DVGs during betacoronavirus evolution, influenced by MOI and cell- and virus-specific factors.

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Section: Discussionmentioning

confidence: 99%

Accumulation dynamics of defective genomes during experimental evolution of two betacoronaviruses

Hillung,

Olmo-Uceda,

Muñoz-Sánchez

et al. 2024

Preprint

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“…Importantly, mRNA conveyed by oEVs was efficiently delivered to target cells and translated into protein. In the target cell, the protein was functional and was able to be presented by APC cells and stimulate a lymphocyte response, detected as the increase in CD4+ proliferating cells and of CD69+, CD25+ and HLADR+ activated cells ( Figure 4 ) [ 35 , 36 ]. These findings suggested the possible efficacy of oEVs as a carrier for mRNA-based vaccines and prompted us to test their effect in mice.…”

Section: Discussionmentioning

confidence: 99%

Plant-Derived Extracellular Vesicles as a Delivery Platform for RNA-Based Vaccine: Feasibility Study of an Oral and Intranasal SARS-CoV-2 Vaccine

Pomatto

Gai

Negro³

et al. 2023

Pharmaceutics

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Plant-derived extracellular vesicles (EVs) may represent a platform for the delivery of RNA-based vaccines, exploiting their natural membrane envelope to protect and deliver nucleic acids. Here, EVs extracted from orange (Citrus sinensis) juice (oEVs) were investigated as carriers for oral and intranasal SARS-CoV-2 mRNA vaccine. oEVs were efficiently loaded with different mRNA molecules (coding N, subunit 1 and full S proteins) and the mRNA was protected from degrading stress (including RNase and simulated gastric fluid), delivered to target cells and translated into protein. APC cells stimulated with oEVs loaded with mRNAs induced T lymphocyte activation in vitro. The immunization of mice with oEVs loaded with S1 mRNA via different routes of administration including intramuscular, oral and intranasal stimulated a humoral immune response with production of specific IgM and IgG blocking antibodies and a T cell immune response, as suggested by IFN-γ production by spleen lymphocytes stimulated with S peptide. Oral and intranasal administration also triggered the production of specific IgA, the mucosal barrier in the adaptive immune response. In conclusion, plant-derived EVs represent a useful platform for mRNA-based vaccines administered not only parentally but also orally and intranasally.

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“…A preventive approach against hepatitis C has been developed, involving the testing of an EV-based vaccine on mice. In particular, the DNA plasmids were used to generate modified retrovirus-like EVs, aiming to confer immune protection against HCV [ 95 ].…”

Section: Functional Gastrointestinal Diseases and Ev-based Therapymentioning

confidence: 99%

Unveiling the Potential of Extracellular Vesicles as Biomarkers and Therapeutic Nanotools for Gastrointestinal Diseases

Arrè,

Mastrogiacomo,

Balestra

et al. 2024

Pharmaceutics

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Extracellular vesicles (EVs), acting as inherent nanocarriers adept at transporting a range of different biological molecules such as proteins, lipids, and genetic material, exhibit diverse functions within the gastroenteric tract. In states of normal health, they participate in the upkeep of systemic and organ homeostasis. Conversely, in pathological conditions, they significantly contribute to the pathogenesis of gastrointestinal diseases (GIDs). Isolating EVs from patients’ biofluids facilitates the discovery of new biomarkers that have the potential to offer a rapid, cost-effective, and non-invasive method for diagnosing and prognosing specific GIDs. Furthermore, EVs demonstrate considerable therapeutic potential as naturally targeted physiological carriers for the intercellular delivery of therapeutic cargo molecules or as nanoscale tools engineered specifically to regulate physio-pathological conditions or disease progression. Their attributes including safety, high permeability, stability, biocompatibility, low immunogenicity, and homing/tropism capabilities contribute to their promising clinical therapeutic applications. This review will delve into various examples of EVs serving as biomarkers or nanocarriers for therapeutic cargo in the context of GIDs, highlighting their clinical potential for both functional and structural gastrointestinal conditions. The versatile and advantageous properties of EVs position them as promising candidates for innovative therapeutic strategies in advancing personalized medicine approaches tailored to the gastroenteric tract, addressing both functional and structural GIDs.

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Extracellular Vesicles and Viruses: Two Intertwined Entities

Cited by 35 publications

References 174 publications

Accumulation dynamics of defective genomes during experimental evolution of two betacoronaviruses

Accumulation dynamics of defective genomes during experimental evolution of two betacoronaviruses

Plant-Derived Extracellular Vesicles as a Delivery Platform for RNA-Based Vaccine: Feasibility Study of an Oral and Intranasal SARS-CoV-2 Vaccine

Unveiling the Potential of Extracellular Vesicles as Biomarkers and Therapeutic Nanotools for Gastrointestinal Diseases

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