Extracellular circulating viral microRNAs: current knowledge and perspectives

Laganà, Alessandro; Russo, Francesco; Veneziano, Dario; Bella, Sebastiano Di; Giugno, Rosalba; Pulvirenti, Alfredo; Croce, Carlo M.; Ferro, Alfredo

doi:10.3389/fgene.2013.00120

Cited by 41 publications

(40 citation statements)

References 91 publications

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“…Some membrane proteins that are typically found in exosomes, such as Alix, TSG101, CD63, CD81, and CD9, can be considered exosome markers (28,29). Some miR-NAs identified within exosomes can cause phenotypic changes in the recipient cells (30,32,42).…”

mentioning

confidence: 99%

Exosomes from uninfected cells activate transcription of latent HIV-1

Barclay

Schwab

DeMarino

et al. 2017

Journal of Biological Chemistry

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HIV-1 infection causes AIDS, infecting millions worldwide. The virus can persist in a state of chronic infection due to its ability to become latent. We have previously shown a link between HIV-1 infection and exosome production. Specifically, we have reported that exosomes transport viral proteins and RNA from infected cells to neighboring uninfected cells. These viral products could then elicit an innate immune response, leading to activation of the Toll-like receptor and NF-κB pathways. In this study, we asked whether exosomes from uninfected cells could activate latent HIV-1 in infected cells. We observed that irrespective of combination antiretroviral therapy, both short- and long-length viral transcripts were increased in wild-type HIV-1-infected cells exposed to purified exosomes from uninfected cells. A search for a possible mechanism for this finding revealed that the exosomes increase RNA polymerase II loading onto the HIV-1 promoter in the infected cells. These viral transcripts, which include trans-activation response (TAR) RNA and a novel RNA that we termed TAR-, can then be packaged into exosomes and potentially be exported to neighboring uninfected cells, leading to increased cellular activation. To better decipher the exosome release pathways involved, we used siRNA to suppress expression of ESCRT (endosomal sorting complex required for transport) proteins and found that ESCRT II and IV significantly control exosome release. Collectively, these results imply that exosomes from uninfected cells activate latent HIV-1 in infected cells and that true transcriptional latency may not be possible , especially in the presence of combination antiretroviral therapy.

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confidence: 99%

Exosomes from uninfected cells activate transcription of latent HIV-1

Barclay

Schwab

DeMarino

et al. 2017

Journal of Biological Chemistry

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“…Shedding vesicles are generated during the surface shedding from the plasma membrane (100-500 nm), while the production of exosomes are totally different, which are derived from multivesicular bodies secreted into extracellular space by exocytosis (30-80 nm) [30]. EVs are presented in not only the medium of cell culture but also most part of body fluids, including serum/plasma, saliva, urine as well as milk, which largely overlaps with where secreted miRNAs were found [31]. In addition, it is reported that EVs contains lipids, cytosolic proteins, messenger RNAs and even miRNAs, indicating miRNAs in EVs may be the main source of that found in body fluids [32].…”

Section: Secreted Micrornas In Extracellular Vesiclesmentioning

confidence: 99%

Roles of extracellular microRNAs in central nervous system

Wang

2019

ExRNA

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MicroRNAs are small non-coding RNAs containing about 18-25 nucleotides which modulate gene expression post-transcriptionally. Recently, microRNAs have been detected in the extracellular space including a wide range of body fluids. These extracellular miRNAs, often encapsulated in secreted extracellular vesicles, can be transferred into recipient cells and thus inhibits the expression of targeted genes. In view of these findings, a new exosome-based therapeutic approach is invented, which can effectively deliver miRNAs/siRNAs into specific cells. In central nervous system, extracellular miRNAs can not only be used as noninvasive biomarkers for diagnosis of several neurological disorders, but also mediate the intercellular communication between neurons and glial cells. In this review, we will discuss the latest research work regarding the roles of secreted miRNAs in central nervous system and evaluate the potential of exosome-mediated miRNAs/siRNAs delivery in neural therapy.

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“…Among DNA viruses, which express the majority of currently known virus-encoded miRNAs, 95% of viral miRNAs identified to date are of herpesvirus origin. 74 Indeed, the first report of virus-encoded miRNAs dates back to 2004 and describes the cloning of viral miRNAs from EBV-infected cells. 75 Since that, viral miRNAs were evidenced to have roles in a variety of pro-tumorigenic process, 67,76,77 although there are relatively few published investigations directly linking viral miRNAs and telomerase regulation.…”

Section: Non-coding Rnas In Telomerase Regulation By Oncogenic Virusesmentioning

confidence: 99%

Tumor Cell Development: A Role for Viruses and Telomerase Activity?

2014

Advances in Tumor Virology

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ABSTRACT:Telomere biology is an important aspect of human cancer, because the telomere dysfunction and telomerase activity are associated with genomic instability and cellular immortalization. In this article, we review the regulation of telomere dynamics and telomerase activity in virus-related cancers. Viruses may exploit these events to favor its replication and, therefore, may differ from non-viral cancers in this regard. Focusing on Epstein-Barr virus (EBV), human papillomavirus (HPV), hepatitis B virus (HBV), and hepatitis C virus (HCV), which concentrate the majority of the evidence regarding telomere biology and viral cancers), although other viruses are more briefly mentioned, it is noticeable that regulatory mechanisms of telomere dynamics and telomerase activity are virus specific. Such mechanisms include accelerated telomere shortening because of higher rates of cellular proliferation, telomerase activity regulation, and activation of alternative lengthening of telomeres (ALT). Additionally, there is also some evidence supporting a role of viral noncoding RNAs (ncRNAs) and virus-induced alterations in host ncRNAs in telomerase activity. Clarification of the roles of telomere biology in mediating viral cancers would have implications only for developing telomere-targeting anti-cancer approaches and, possibly, to accelerate advances in other telomererelated diseases, such as non-viral cancers and other aging traits.

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Extracellular circulating viral microRNAs: current knowledge and perspectives

Cited by 41 publications

References 91 publications

Exosomes from uninfected cells activate transcription of latent HIV-1

Exosomes from uninfected cells activate transcription of latent HIV-1

Roles of extracellular microRNAs in central nervous system

Tumor Cell Development: A Role for Viruses and Telomerase Activity?

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