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Review
. 2020 May 22;12(5):571.
doi: 10.3390/v12050571.

The Role of Extracellular Vesicles as Allies of HIV, HCV and SARS Viruses

Flavia Giannessi  1 , Alessandra Aiello  1 , Francesca Franchi  1 , Zulema Antonia Percario  1 , Elisabetta Affabris  1
Affiliations
Review

The Role of Extracellular Vesicles as Allies of HIV, HCV and SARS Viruses

Flavia Giannessi et al. Viruses. .

Abstract

Extracellular vesicles (EVs) are lipid bilayer-enclosed entities containing proteins and nucleic acids that mediate intercellular communication, in both physiological and pathological conditions. EVs resemble enveloped viruses in both structural and functional aspects. In full analogy with viral biogenesis, some of these vesicles are generated inside cells and, once released into the extracellular milieu, are called "exosomes". Others bud from the plasma membrane and are generally referred to as "microvesicles". In this review, we will discuss the state of the art of the current studies on the relationship between EVs and viruses and their involvement in three important viral infections caused by HIV, HCV and Severe Acute Respiratory Syndrome (SARS) viruses. HIV and HCV are two well-known pathogens that hijack EVs content and release to create a suitable environment for viral infection. SARS viruses are a new entry in the world of EVs studies, but are equally important in this historical framework. A thorough knowledge of the involvement of the EVs in viral infections could be helpful for the development of new therapeutic strategies to counteract different pathogens.

Keywords: HCV; HIV; SARS viruses; coronaviruses; exosomes; extracellular vesicles.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
EVs are vehicles for the communication between infected and uninfected cells. During viral infections, virus enters cells and exploits the vesicular biogenesis machinery to release EVs, microvesicles (MV) and exosomes (Exo) with a modified composition to favor its own pathogenesis. EVs can carry (a) entire viral particles; (b) different viral proteins, such as the envelope ones; (c) nucleic acids including viral genomes, microRNAs and small non-coding RNAs and (d) host cell proteins, whose production is induced by the virus. Finally, EVs are internalized through different mechanisms and their luminal content released into the cytosol of the recipient cells. Nucleus (N); endoplasmic reticulum (ER); Golgi complex (G); multivesicular bodies (MVB); intraluminal vesicles (ILVs).
Figure 2
Figure 2
Schematic representation of EVs released by HIV-infected cells. EVs derived from HIV-infected cells carry both viral and host cell components that favor viral spreading and HIV-associated immune pathogenesis. Regarding host proteins, EVs transfer the two co-receptors CCR5 and CXCR4, used by the virus to mediate its entry, to null cells. Among viral components, EVs carry the proteins Gag, gp120 and Nef, as well as Trans-Activation Response (TAR) RNA, a pre-microRNA that produces mature microRNAs. Nef protein also induces the uploading into EVs of ADAM17/TACE, a TNFα converting enzyme. Nucleus (N); endoplasmic reticulum (ER); Golgi complex (G).
Figure 3
Figure 3
Schematic representation of EVs released by HCV-infected cells. EVs derived from HCV-infected cells carry both viral and host cell components that promote viral dissemination and immune pathogenesis. HCV-EVs carry entire viral particles, thus hiding them to immune system and allowing the virus to enter the recipient cells using uncanonical receptors. In addition, HCV-EVs transfer the glycoproteins E1 and E2, viral genomes as well as miRNAs, such as miRNA-19a, miRNA-192 and miRNA-122, and host proteins including Argonaute 2 (Ago2), the effector of RNA interference (RNAi) that associates with Hsp90. Nucleus (N); endoplasmic reticulum (ER); Golgi complex (G).
Figure 4
Figure 4
Schematic representation of EVs released by coronavirus (CoV)-infected cells. CoVs hijack the cellular machinery to favor their replication. CoVs proteins promote the formation into the cytosol of double-membrane vesicles (DMVs) that are associated to the replication and transcription complexes (RTCs) where the viral replication occurs. After the production of structural and non-structural proteins, the budding can take place from Golgi and ER membranes. Subsequently, viral particles are released into the extracellular space by exploiting the vesicular network. In addition to viral particles, CoVs induce the release of vesicles carrying the viral envelope (E) and membrane (M) proteins. To date, there are not clear evidences of vesicles released by CoV-infected cells transporting other viral or host factors. Nucleus (N); endoplasmic reticulum (ER); Golgi complex (G).
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References

    1. Raposo G., Stoorvogel W. Extracellular vesicles: Exosomes, microvesicles, and friends. J. Cell Biol. 2013;200:373–383. doi: 10.1083/jcb.201211138. - DOI - PMC - PubMed
    1. Altan-Bonnet N. Extracellular vesicles are the Trojan horses of viral infection. Curr. Opin. Microbiol. 2016;32:77–81. doi: 10.1016/j.mib.2016.05.004. - DOI - PMC - PubMed
    1. Pisitkun T., Shen R.-F., Knepper M.A. Identification and proteomic profiling of exosomes in human urine. Proc. Natl. Acad. Sci. USA. 2004;101:13368–13373. doi: 10.1073/pnas.0403453101. - DOI - PMC - PubMed
    1. Keller S., Ridinger J., Rupp A.-K., Janssen J.W.G., Altevogt P. Body fluid derived exosomes as a novel template for clinical diagnostics. J. Transl. Med. 2011;9:86. doi: 10.1186/1479-5876-9-86. - DOI - PMC - PubMed
    1. Caby M.-P., Lankar D., Vincendeau-Scherrer C., Raposo G., Bonnerot C. Exosomal-like vesicles are present in human blood plasma. Int. Immunol. 2005;17:879–887. doi: 10.1093/intimm/dxh267. - DOI - PubMed

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