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Direct Stochastic Optical Reconstruction Microscopy of Extracellular Vesicles in Three Dimensions
Published on: August 26, 2021
Neural stem cell-derived exosomes mediate viral entry
Brian Sims1, Linlin Gu2, Alexandre Krendelchtchikov2
1Division of Neonatology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA ; Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL, USA.
Background:
Viruses enter host cells through interactions of viral ligands with cellular receptors. Viruses can also enter cells in a receptor-independent fashion. Mechanisms regarding the receptor-independent viral entry into cells have not been fully elucidated. Exosomal trafficking between cells may offer a mechanism by which viruses can enter cells.
Methods:
To investigate the role of exosomes on cellular viral entry, we employed neural stem cell-derived exosomes and adenovirus type 5 (Ad5) for the proof-of-principle study.
Results:
Exosomes significantly enhanced Ad5 entry in Coxsackie virus and adenovirus receptor (CAR)-deficient cells, in which Ad5 only had very limited entry. The exosomes were shown to contain T-cell immunoglobulin mucin protein 4 (TIM-4), which binds phosphatidylserine. Treatment with anti-TIM-4 antibody significantly blocked the exosome-mediated Ad5 entry.
Conclusion:
Neural stem cell-derived exosomes mediated significant cellular entry of Ad5 in a receptor-independent fashion. This mediation may be hampered by an antibody specifically targeting TIM-4 on exosomes. This set of results will benefit further elucidation of virus/exosome pathways, which would contribute to reducing natural viral infection by developing therapeutic agents or vaccines.
Insights
Neural stem cell-derived exosomes facilitate virus entry into cells independently of cellular receptors. Targeting TIM-4 on exosomes can block this receptor-independent viral entry, offering new therapeutic avenues.
Area of Science:
- Virology
- Cell Biology
- Nanomedicine
Background:
- Viruses typically enter host cells via receptor-ligand interactions.
- Receptor-independent viral entry mechanisms remain incompletely understood.
- Exosomal trafficking presents a potential pathway for virus cell entry.
Purpose of the Study:
- To investigate the role of exosomes in mediating cellular viral entry.
- To explore exosome-mediated, receptor-independent viral entry using adenovirus type 5 (Ad5).
Main Methods:
- Utilized neural stem cell-derived exosomes and Ad5 for proof-of-principle experiments.
- Assessed Ad5 entry into Coxsackie virus and adenovirus receptor (CAR)-deficient cells.
- Analyzed exosome composition for viral entry mediators and tested blocking antibodies.
Main Results:
- Exosomes significantly enhanced Ad5 entry into CAR-deficient cells.
- Exosomes were found to contain T-cell immunoglobulin mucin protein 4 (TIM-4).
- Anti-TIM-4 antibody treatment blocked exosome-mediated Ad5 entry.
Conclusions:
- Neural stem cell-derived exosomes mediate Ad5 cellular entry in a receptor-independent manner.
- TIM-4 on exosomes appears crucial for this entry mechanism.
- Findings support the development of therapeutics or vaccines targeting virus-exosome pathways.
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