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Review
. 2017 Apr;36(4):243-248.
doi: 10.1089/dna.2017.3639. Epub 2017 Feb 8.

The Role of Exosomal VP40 in Ebola Virus Disease

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Free PMC article
Review

The Role of Exosomal VP40 in Ebola Virus Disease

Michelle L Pleet et al. DNA Cell Biol. .
Free PMC article

Abstract

Ebola virus (EBOV) can cause a devastating hemorrhagic disease, leading to death in a short period of time. After infection, the resulting EBOV disease results in high levels of circulating cytokines, endothelial dysfunction, coagulopathy, and bystander lymphocyte apoptosis in humans and nonhuman primates. The VP40 matrix protein of EBOV is essential for viral assembly and budding from the host cell. Recent data have shown that VP40 exists in the extracellular environment, including in exosomes, and exosomal VP40 can impact the viability of recipient immune cells, including myeloid and T cells, through the regulation of the RNAi and endosomal sorting complexes required for transport pathways. In this study, we discuss the latest findings of the impact of exosomal VP40 on immune cells in vitro and its potential implications for pathogenesis in vivo.

Keywords: ESCRT; Ebola; RNAi; VP40; apoptosis; exosomes.

Conflict of interest statement

No competing financial interests exist.

Figures

<b>FIG. 1.</b>
FIG. 1.
Impact of exosomes containing Ebola VP40 on recipient immune cells. Ebola VP40 protein becomes integrated into exosomes with the modulation of ESCRT pathway components. Upon release, these exosomes can be received by immune cells (i.e., T cells). RNAi components, including Drosha, Dicer, and Ago, in both exosome donor and recipient cells can become downregulated. Recipient immune cells can then take part in programmed cell death. Nanoparticles may be used for the concentration of exosomes to detect viral proteins (and potentially RNAs) from samples, including human material using SDS buffer. ESCRT, endosomal sorting complexes required for transport; SDS, sodium dodecyl sulfate.
<b>FIG. 2.</b>
FIG. 2.
Potential role of exosomes containing Ebola VP40 in viral persistence. Infected cells in immune privileged sites (i.e., ocular fluid) could release exosomes containing viral proteins such as VP40. These exosomes may then travel to distant areas such as lymph nodes, where they may induce apoptosis in immune and T cell populations. Increased cell death in surveilling immune cells could allow for increased viral replication and persistence in local compartments.

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