Extracellular vesicles from Kaposi Sarcoma-associated herpesvirus lymphoma induce long-term endothelial cell reprogramming

McNamara, Ryan P.; Chugh, Pauline; Bailey, Aubrey; Costantini, Lindsey M.; Ma, Zhe; Bigi, Rachele; Cheves, Avery; Eason, Anthony; Landis, Justin T.; Host, Kurtis M.; Xiong, Jessie; Griffith, Jack D.; Damania, Blossom; Dittmer, Dirk P.

doi:10.1371/journal.ppat.1007536

Cited by 47 publications

(76 citation statements)

References 70 publications

(93 reference statements)

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“…They are rare but can spread through blood and have proven life-threatening. Kaposi’s sarcoma-associated herpesvirus (KSHV) is shown to change the microenvironment by utilizing the host-derived exosomes [ 80 ]. Epidermal growth factor receptor plays an important role in the infection of KSHV, and this is promoted by the exosomes associated with HIV [ 81 ].…”

Section: Eye Cancersmentioning

confidence: 99%

Exosomes: Insights from Retinoblastoma and Other Eye Cancers

Lande

Gupta

Ranjan

et al. 2020

IJMS

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Exosomes, considered as cell debris or garbage bags, have been later characterized as nanometer-sized extracellular double-membrane lipid bilayer bio-vesicles secreted by the fusion of vesicular bodies with the plasma membrane. The constituents and the rate of exosomes formation differ in different pathophysiological conditions. Exosomes are also observed and studied in different parts of the eye, like the retina, cornea, aqueous, and vitreous humor. Tear fluid consists of exosomes that are shown to regulate various cellular processes. The role of exosomes in eye cancers, especially retinoblastoma (RB), is not well explored, although few studies point towards their presence. Retinoblastoma is an intraocular tumor that constitutes 3% of cases of cancer in children. Diagnosis of RB may require invasive procedures, which might lead to the spread of the disease to other parts. Due to this reason, better ways of diagnosis are being explored. Studies on the exosomes in RB tumors and serum might help designing better diagnostic approaches for RB. In this article, we reviewed studies on exosomes in the eye, with a special emphasis on RB. We also reviewed miRNAs expressed in RB tumor, serum, and cell lines and analyzed the targets of these miRNAs from the proteins identified in the RB tumor exosomes. hsa-miR-494 and hsa-miR-9, upregulated and downregulated, respectively in RB, have the maximum number of targets. Although oppositely regulated, they share the same targets in the proteins identified in RB tumor exosomes. Overall this review provides the up-to-date progress in the area of eye exosome research, with an emphasis on RB.

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Section: Eye Cancersmentioning

confidence: 99%

Exosomes: Insights from Retinoblastoma and Other Eye Cancers

Lande

Gupta

Ranjan

et al. 2020

IJMS

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“…Much work is still necessary to fully uncover the depth to which miRNAs influence the fate of viral RNAs and the physiological consequences of this activity. Several studies have reported functions for miRNAs far beyond this scope, especially with reports describing their incorporation into extracellular vesicles and even KSHV virions for signaling in a paracrine like manner [94,95]. With these findings in mind, several questions remain regarding what cellular and viral factors drive the expression of miRNAs and why their expression levels vary drastically between KSHV life cycle stages and tissue-derived samples.…”

Section: Rna Decaymentioning

confidence: 99%

Stealing the Show: KSHV Hijacks Host RNA Regulatory Pathways to Promote Infection

Macveigh-Fierro

Rodríguez

Miles

et al. 2020

Viruses

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Kaposi’s sarcoma-associated herpesvirus (KSHV) induces life-long infections and has evolved many ways to exert extensive control over its host’s transcriptional and post-transcriptional machinery to gain better access to resources and dampened immune sensing. The hallmark of this takeover is how KSHV reshapes RNA fate both to control expression of its own gene but also that of its host. From the nucleus to the cytoplasm, control of RNA expression, localization, and decay is a process that is carefully tuned by a multitude of factors and that can adapt or react to rapid changes in the environment. Intriguingly, it appears that KSHV has found ways to co-opt each of these pathways for its own benefit. Here we provide a comprehensive review of recent work in this area and in particular recent advances on the post-transcriptional modifications front. Overall, this review highlights the myriad of ways KSHV uses to control RNA fate and gathers novel insights gained from the past decade of research at the interface of RNA biology and the field of KSHV research.

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“…Bead-based purification efficiency depends on antibody affinity, availability, and ligand density on viruses or EV surface [ 30 ]. This technique rapidly and successfully enriched and separated marker-positive EV from viruses, and other EV which did not carry the specific marker and allowed the identification of exosome enclosed RNAs and proteins [ 32 , 33 , 36 , 46 , 47 ].…”

Section: How Do Rnas Co-purify With Viruses and Ev By Different Pumentioning

confidence: 99%

“…Despite many studies, the mechanisms for incorporating mRNA and non-coding RNA into virions remains incompletely understood and is subject to intense debate. The biological roles that the EV-mediated transfer of RNAs plays in viral pathogenesis are just beginning to emerge, for example in human herpesviruses [ 36 , 46 , 74 , 75 , 76 ]. Insights derived from the virus-mediated transfer of intact RNAs could, therefore, provide an example for EV-mediated transfer of functional RNA.…”

Section: Do Dna Viruses Package Rnas In Virus Particles?mentioning

confidence: 99%

“…For instance, high levels of EBV BHRF1 and BART cluster viral miRNAs were transferred to monocyte-derived dendritic cells to repress target genes [ 75 ]. In KSHV infected cells, viral miRNAs can modulate the tumor microenvironment by shifting the metabolic patterns toward aerobic glycolysis [ 90 ] and can induce long-term endothelial cell reprogramming [ 46 ]. HCV-infected hepatocytes secrete miRNA-containing EV to mediate the activation of hepatic stellate cells (HSC) that cause liver fibrosis [ 84 , 85 ].…”

Section: How Many Mirnas Are In An Exosome?mentioning

confidence: 99%

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Purification Methods and the Presence of RNA in Virus Particles and Extracellular Vesicles

Zhou

McNamara

Dittmer

2020

Viruses

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The fields of extracellular vesicles (EV) and virus infections are marred in a debate on whether a particular mRNA or non-coding RNA (i.e., miRNA) is packaged into a virus particle or copurifying EV and similarly, whether a particular mRNA or non-coding RNA is contained in meaningful numbers within an EV. Key in settling this debate, is whether the purification methods are adequate to separate virus particles, EV and contaminant soluble RNA and RNA:protein complexes. Differential centrifugation/ultracentrifugation and precipitating agents like polyethylene glycol are widely utilized for both EV and virus purifications. EV are known to co-sediment with virions and other particulates, such as defective interfering particles and protein aggregates. Here, we discuss how encased RNAs from a heterogeneous mixture of particles can be distinguished by different purification methods. This is particularly important for subsequent interpretation of whether the RNA associated phenotype is contributed solely by virus or EV particles or a mixture of both. We also discuss the discrepancy of miRNA abundance in EV from different input material.

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Extracellular vesicles from Kaposi Sarcoma-associated herpesvirus lymphoma induce long-term endothelial cell reprogramming

Cited by 47 publications

References 70 publications

Exosomes: Insights from Retinoblastoma and Other Eye Cancers

Exosomes: Insights from Retinoblastoma and Other Eye Cancers

Stealing the Show: KSHV Hijacks Host RNA Regulatory Pathways to Promote Infection

Purification Methods and the Presence of RNA in Virus Particles and Extracellular Vesicles

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