https://doi.org/10.3389/fmicb.2015.01132
Extracellular vesicles from infected cells: potential for direct pathogenesis
Infections that result in natural or manmade spread of lethal biological agents are a concern and require national and focused preparedness. In this manuscript, as part of an early diagnostics and pathogen treatment strategy, we have focused on extracellular vesicles (EVs) that arise following infections. Although the field of biodefense does not currently have a rich resource in EVs literature, none the less, similar pathogens belonging to the more classical emerging and non-emerging diseases have been studied in their EV/exosomal contents and function. These exosomes are formed in late endosomes and released from the cell membrane in almost every cell type in vivo. These vesicles contain proteins, RNA, and lipids from the cells they originate from and function in development, signal transduction, cell survival, and transfer of infectious material. The current review focuses on how different forms of infection exploit the exosomal pathway and how exosomes can be exploited artificially to treat infection and disease and potentially also be used as a source of vaccine. Virally-infected cells can secrete viral as well as cellular proteins and RNA in exosomes, allowing viruses to cause latent infection and spread of miRNA to nearby cells prior to a subsequent infection. In addition to virally-infected host cells, bacteria, protozoa, and fungi can all release small vesicles that contain pathogen-associated molecular patterns, regulating the neighboring uninfected cells. Examples of exosomes from both virally and bacterially infected cells point toward a re-programming network of pathways in the recipient cells. Finally, many of these exosomes contain cytokines and miRNAs that in turn can effect gene expression in the recipient cells through the classical toll-like receptor and NFκB pathway. Therefore, although exosomes do not replicate as an independent entity, they however facilitate movement of infectious material through tissues and may be the cause of many pathologies seen in infected hosts.
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DNA Viruses
Epstein-Barr Virus
The EBV is a large DNA virus associated with B-cell lymphomas and carcinomas in tongue, nasopharynx, and stomach. The virus is found in a latent stage in both lymphomas and carcinomas (Morales-Sanchez and Fuentes-Panana, 2014). The presence of oncoproteins and viral miRNAs in exosomes from EBV-infected cells gives credence to the fact that virus-infected cells use the exosomal pathway to regulate gene expression in the surrounding tissue to avert destruction by the immune system....
Herpesvirus
The role of protein transfer from intracellular compartments to exosomes has also been studied in Herpes-simplex virus-1 (HSV-1) infected cells. Temme et al. (2010), have shown that the HSV-1 encoded glycoprotein B (gB) manipulates class II processing pathway by perturbing endosomal sorting and trafficking of HLA-DR (DR) molecules....
Interestingly, the human herpes virus 6 (HHV-6) induces formation of multivesicular bodies (MVBs; Mori et al., 2008). In ILVs contained in these MVBs, HHV-6–derived glycoproteins B and M were detected. HHV-6 uses the cellular exosomal pathway of the host cell for exiting the cell....
RNA Viruses
HIV/HTLV Infection
...Similar to other pathogens, retroviruses hijack exosomal proteins as well as other components to increase their spread throughout the body. In addition to this benefit, the resulting changes in recipient cells can be profound leading to disease state and pathologies associated with an infection. To this end, HIV-1 infected macrophages have been shown to have increased number of exosomes and other vesicles secreted from the cell (Kadiu and Gendelman, 2011a,b; Kadiu et al., 2011, 2012). Importantly, these exosomes have been shown to contain various cytokines that induce migration and release of other inflammatory cytokines from recipient cells leading to enhanced HIV-1 infectivity....
