Oncoviral Infections and Small Extracellular Vesicles

Abstract

Small extracellular vesicles (sEV) are small membrane-bound nanovesicles with a size range below 200 nm that are released by all types of cells. sEV carry a diverse cargo of proteins, lipids, glycans, and nucleic acids that mimic the content of producer cells. sEV mediate intercellular communication and play a key role in a broad variety of physiological and pathological conditions. Recently, numerous reports have emerged examining the role of sEV in viral infections. A significant number of similarities in the sEV biogenesis pathways and the replication cycles of viruses suggest that sEV might influence the course of viral infections in diverse ways. Besides directly modulating virus propagation by transporting the viral cargo (complete virions, proteins, RNA, and DNA), sEV can also modify the host antiviral response and increase the susceptibility of cells to infection. The network of mutual interactions is particularly complex in the case of oncogenic viruses, deserving special consideration because of its significance in cancer progression. This review summarizes the current knowledge of interactions between sEV and oncogenic viruses, focusing on sEV abilities to modulate the carcinogenic properties of oncoviruses.

Keywords: exosomes; oncoviruses; small extracellular vesicles (sEV); viral infections.

Figure 1

The influence of small extracellular vesicles (sEV) in viral infections. sEV can promote (A) or inhibit viral infections (B). The mechanisms underlying the sEV ability to facilitate viral infections are multifaceted, including the transmission of viral cargo, the delivery of entry receptors for the virus to new cells, and the binding of neutralizing antibodies. On the other hand, sEV antiviral effects are associated with the delivery of host restriction factors, such as APOBEC3G (apolipoprotein B mRNA editing enzyme catalytic subunit 3G) and IFTIM3 (interferon-induced transmembrane protein 3), as well as miRNAs that condition immunity to infection. sEV can also bind to virions (the „bait” mechanism), induce antiviral immune responses by delivering viral pathogen-associated molecular patterns (PAMPs) to antigen presenting cells (APCs), and promote the activation of natural killer cells (NK cells) and proliferation of CD4+ and CD8+ T cells. Created with BioRender.com.

Figure 2

Role of sEV in HBV infection and the development of HBV-induced liver disease. sEV secreted from HBV-infected cells transport bioactive cargo and may promote progression of HBV-dependent HCC. Created with BioRender.com.