Extracellular RNA in viral–host interactions: Thinking outside the cell

Ressel, Sarah; Roșca, Adelina; Gordon, Katrina E.; Buck, Amy H.

doi:10.1002/wrna.1535

Cited by 17 publications

(12 citation statements)

References 213 publications

(290 reference statements)

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“…In systemic alteration of an immune response, major regulators commonly known as specifically enriched micro RNAs (miRNAs) are delivered by EVs. These are loaded into EVs and are involved in post-transcriptional regulation of gene expression, which is known to be influential for HCV replication [176,177]. This confirms that EVs have peculiar miRNA expression isolated from the sera of chronic HCV patients.…”

Section: Hepatitis C Virus and Evssupporting

confidence: 53%

Extracellular Vesicles in Viral Replication and Pathogenesis and Their Potential Role in Therapeutic Intervention

Kumar

Tadrous

et al. 2020

Viruses

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Extracellular vesicles (EVs) have shown their potential as a carrier of molecular information, and they have been involved in physiological functions and diseases caused by viral infections. Virus-infected cells secrete various lipid-bound vesicles, including endosome pathway-derived exosomes and microvesicles/microparticles that are released from the plasma membrane. They are released via a direct outward budding and fission of plasma membrane blebs into the extracellular space to either facilitate virus propagation or regulate the immune responses. Moreover, EVs generated by virus-infected cells can incorporate virulence factors including viral protein and viral genetic material, and thus can resemble noninfectious viruses. Interactions of EVs with recipient cells have been shown to activate signaling pathways that may contribute to a sustained cellular response towards viral infections. EVs, by utilizing a complex set of cargos, can play a regulatory role in viral infection, both by facilitating and suppressing the infection. EV-based antiviral and antiretroviral drug delivery approaches provide an opportunity for targeted drug delivery. In this review, we summarize the literature on EVs, their associated involvement in transmission in viral infections, and potential therapeutic implications.

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Section: Hepatitis C Virus and Evssupporting

confidence: 53%

Extracellular Vesicles in Viral Replication and Pathogenesis and Their Potential Role in Therapeutic Intervention

Kumar

Tadrous

et al. 2020

Viruses

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“…They are released by donor cells into their surrounding environment. EVs have been extensively characterized in animals and humans, where they are classified based on their size and origins: exosomes, which are 30 to 100 nm in diameter; shedding microvesicles, which are 100 nm to 1 mm in diameter; and apoptotic bodies, which are 50 nm to 5 mm in diameter (Théry et al, 2009;Ressel et al, 2019). Microvesicles are shed from the plasma membrane; apoptotic bodies contain parts of dying cells formed during programmed cell death; and exosomes are formed in the cytosol by inward budding of the limiting membrane of endocytic compartments, leading to vesicle-containing endosomes called multivesicular bodies (MVBs).…”

Section: Mechanism(s) Of Srna Movement Between Pathogens and Plant Cellsmentioning

confidence: 99%

“…Microvesicles are shed from the plasma membrane; apoptotic bodies contain parts of dying cells formed during programmed cell death; and exosomes are formed in the cytosol by inward budding of the limiting membrane of endocytic compartments, leading to vesicle-containing endosomes called multivesicular bodies (MVBs). The vesicles are released into the environment when MVBs fuse with the plasma membrane (Raposo and Stoorvogel, 2013;Ressel et al, 2019). EVs have been shown to be key players in intercellular communication in animal systems.…”

Section: Mechanism(s) Of Srna Movement Between Pathogens and Plant Cellsmentioning

confidence: 99%

Exchange of Small Regulatory RNAs between Plants and Their Pests

Hudzik

Hou

et al. 2019

Plant Physiol.

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Regulatory small RNAs are well known as antiviral agents, regulators of gene expression, and defenders of genome integrity in plants. Several studies over the last decade have also shown that some small RNAs are exchanged between plants and their pathogens and parasites. Naturally occurring trans-species small RNAs are used by host plants to silence mRNAs in pathogens. These gene-silencing events are thought to be detrimental to the pathogen and beneficial to the host. Conversely, trans-species small RNAs from pathogens and parasites are deployed to silence host mRNAs; these events are thought to be beneficial for the pests. The natural ability of plants to exchange small RNAs with invading eukaryotic organisms can be exploited to provide disease resistance. This review gives an overview of the current state of trans-species small RNA research in plants and discusses several outstanding questions for future research. SMALL REGULATORY RNA BACKGROUND Small regulatory RNAs (sRNAs) are numerous in plants. They usually range in size from 21 to 24 nucleotides and serve as key regulators of gene expression. sRNAs are involved in myriad processes, including development, cell type designation, responses to abiotic stress, and silencing of repetitive elements. sRNAs are processed from longer precursor RNAs (either the helical stem regions of self-complementary singlestranded RNAs or double-stranded RNAs [dsRNAs]) by endonucleases in the Dicer-like (DCL) protein family. DCL endonucleases produce an initial short duplex RNA. One of the two short RNA strands forms a complex with a protein in the Argonaute (AGO) family. The AGO-sRNA complex then identifies target RNAs based on complementarity between target and sRNA. sRNAs can be categorized based on differences in their biogenesis and differences in their modes of targeting (Fig. 1). MicroRNAs (miRNAs) in plants are processed from RNA polymerase II-transcribed primary RNAs. A region of the primary transcript forms an imperfect hairpin structure that is recognized by the DCL1 endonuclease. DCL1, along with several accessory proteins, liberates a miRNA/miRNA* duplex. The duplex is disassembled, with the mature miRNA becoming bound to an Argonaute (AGO) protein, most frequently AGO1. Once the mature miRNA is bound to an AGO protein, the miRNA* is typically separated from the complex and degraded (for a more detailed review of plant miRNA biogenesis, see Rogers and Chen, 2013). The resulting miRNA/AGO complex directs posttranscriptional regulation of mRNAs and long noncoding RNAs. Target selection is primarily based on complementarity between the miRNA and target RNA

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“…We found that T. vaginalis EVs deliver proteins and RNA into host cells via unknown mechanisms and modulate parasite adherence to host cells and host cell metabolism (14,15). EVs produced by several parasites have now been described to module host cell metabolism in many ways (16)(17)(18)(19), including the transfer of virulence factors (20), drug resistance markers (21), and microRNAs that downregulate host cell proteins (22)(23)(24). Pathogen EVs have also been shown to affect host cell proliferation (24,25) and neuronal metabolism (26) and to modulate host immune responses (17,23,24,(27)(28)(29).…”

mentioning

confidence: 99%

Trichomonas vaginalis extracellular vesicles are internalized by host cells using proteoglycans and caveolin-dependent endocytosis

Kumar

Johnson

2019

Proc. Natl. Acad. Sci. U.S.A.

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Trichomonas vaginalis, a human-infective parasite, causes the most prevalent nonviral sexually transmitted infection worldwide. This pathogen secretes extracellular vesicles (EVs) that mediate its interaction with host cells. Here, we have developed assays to study the interface between parasite EVs and mammalian host cells and to quantify EV internalization by mammalian cells. We show that T. vaginalis EVs interact with glycosaminoglycans on the surface of host cells and specifically bind to heparan sulfate (HS) present on host cell surface proteoglycans. Moreover, competition assays using HS or removal of HS from the host cell surface strongly inhibit EV uptake, directly demonstrating that HS proteoglycans facilitate EV internalization. We identified an abundant protein on the surface of T. vaginalis EVs, 4-α-glucanotransferase (Tv4AGT), and show using isothermal titration calorimetry that this protein binds HS. Tv4AGT also competitively inhibits EV uptake, defining it as an EV ligand critical for EV internalization. Finally, we demonstrate that T. vaginalis EV uptake is dependent on host cell cholesterol and caveolin-1 and that internalization proceeds via clathrin-independent, lipid raft-mediated endocytosis. These studies reveal mechanisms used to drive host:pathogen interactions and further our understanding of how EVs are internalized by target cells to allow cross-talk between different cell types.

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Extracellular RNA in viral–host interactions: Thinking outside the cell

Cited by 17 publications

References 213 publications

Extracellular Vesicles in Viral Replication and Pathogenesis and Their Potential Role in Therapeutic Intervention

Extracellular Vesicles in Viral Replication and Pathogenesis and Their Potential Role in Therapeutic Intervention

Exchange of Small Regulatory RNAs between Plants and Their Pests

Trichomonas vaginalis extracellular vesicles are internalized by host cells using proteoglycans and caveolin-dependent endocytosis

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