Exosomes and Their Role in the Life Cycle and Pathogenesis of RNA Viruses

Abstract

Exosomes are membrane-enclosed vesicles actively released into the extracellular space, whose content reflect the physiological/pathological state of the cells they originate from. These vesicles participate in cell-to-cell communication and transfer of biologically active proteins, lipids, and RNAs. Their role in viral infections is just beginning to be appreciated. RNA viruses are an important class of pathogens and affect millions of people worldwide. Recent studies on Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV), human T-cell lymphotropic virus (HTLV), and Dengue Virus (DENV) have demonstrated that exosomes released from infected cells harbor and deliver many regulatory factors including viral RNA and proteins, viral and cellular miRNA, and other host functional genetic elements to neighboring cells, helping to establish productive infections and modulating cellular responses. Exosomes can either spread or limit an infection depending on the type of pathogen and target cells, and can be exploited as candidates for development of antiviral or vaccine treatments. This review summarizes recent progress made in understanding the role of exosomes in RNA virus infections with an emphasis on their potential contribution to pathogenesis.

Assembly and release of infectious hepatitis C virus involving unusual organization of the secretory pathway

“…The associations to lipoprotein particles and extracellular particles have been proposed as mechanisms to regulate vertebrate Hedgehog dispersion during development [79] . In addition, ApoE [25,80] and extracellular particles [47] are suspected to contribute also to the pathogenesis of viruses unrelated to HCV. Therefore, rather than having evolved a unique mechanism of viral propagation, HCV may have instead subverted existing cellular processes.…”

“…Albeit incomplete, the siRNA effect on CANX expression was sufficient to abolish BHK-WNV permissiveness for HCV production ( Figure 3C, top panels). Hsp70 or Hsp90 were chosen as controls since they associate with exosomes [46,47] , which are particulate materials secreted by BHK cells yet distinct from HCV particles [8] . After a treatment of BHK-WNV cells with α-TUB siRNA, the releases of Hsp70-and HSp90-containing particles in the supernatant decreased ( Figure 3B and C, bottom panels), in accordance with the requirement for a functional cellular traffic to release exosomes and consistent with an accumulation of Hsp70 in the producer cells.…”

Implication of cell-in-cell structures in the transmission of HIV to epithelial cells

“…However, CD4-negative cells, such as colon ECs and vaginal ECs, were also found to contain HIV and are believed to serve as another productive reservoir [6], suggesting the existence of CD4-independent virus spreading mechanism. Exosomes released from HIV-infected host cells have been reported to facilitate productive HIV infection in non-susceptible cells by delivering cargos such as virus proteins and RNA species [7]. Based on our previous discovery of EBV in-cell infection [2], we hypothesized that formation of heterotypic cell-in-cell structures could also lead to transmission of HIV from internalized CD4 + T cells to the non-susceptible ECs.…”

Exosomes in Viral Disease

“…For the purposes of this review, we will focus our discussion on exosomes; however, there are several excellent reviews in the literature that address Electronic supplementary material The online version of this article (doi:10.1007/s13311-016-0450-6) contains supplementary material, which is available to authorized users. extracellular vesicles as a whole [6][7][8][9][10][11]. In appearance, exosomes are unilamellar vesicles composed of a lipid bilayer that have a homogenous cup-shaped appearance on scanning electromicroscopy [3,12].…”