Exosome-mediated transmission of hepatitis C virus between human hepatoma Huh7.5 cells

Ramakrishnaiah, Vedashree; Thumann, Christine; Fofana, Isabel; Habersetzer, François; Pan, Qiuwei; Ruiter, Petra E. de; Willemsen, Rob; Demmers, Jeroen; Raj, V. Stalin; Jenster, Guido; Kwekkeboom, Jaap; Tilanus, Hugo W.; Haagmans, Bart L.; Baumert, Thomas F.; Laan, Luc J. W. van der

doi:10.1073/pnas.1221899110

Cited by 440 publications

(428 citation statements)

References 29 publications

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“…For whole-mount analysis, EV suspensions (5 µL each) were incubated for 1 min on formvar and carbon-coated glow-discharged copper grids and subsequently stained with 2% uranyl acetate. Immunogold labelling was performed as described [22–24]. After blocking with 1% BSA in phosphate-buffered saline, grids were incubated with a 1:50 dilution of primary mouse anti-CD63 antibody (Thermo Fisher Scientific; TS63) in PBS containing 0.1% BSA for 1 h at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Selective release of circRNAs in platelet‐derived extracellular vesicles

Preußer

Hung

Schneider

et al. 2018

J of Extracellular Vesicle

196

145

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Circular RNAs (circRNAs) are a novel class of noncoding RNAs present in all eukaryotic cells investigated so far and generated by a special mode of alternative splicing of pre-mRNAs. Thereby, single exons, or multiple adjacent and spliced exons, are released in a circular form. CircRNAs are cell-type specifically expressed, are unusually stable, and can be found in various body fluids such as blood and saliva. Here we analysed circRNAs and the corresponding linear splice isoforms from human platelets, where circRNAs are particularly abundant, compared with other hematopoietic cell types. In addition, we isolated extracellular vesicles from purified and in vitro activated human platelets, using density-gradient centrifugation, followed by RNA-seq analysis for circRNA detection. We could demonstrate that circRNAs are packaged and released within both types of vesicles (microvesicles and exosomes) derived from platelets. Interestingly, we observed a selective release of circRNAs into the vesicles, suggesting a specific sorting mechanism. In sum, circRNAs represent yet another class of extracellular RNAs that circulate in the body and may be involved in signalling pathways. Since platelets are essential for central physiological processes such as haemostasis, wound healing, inflammation and cancer metastasis, these findings should greatly extend the potential of circRNAs as prognostic and diagnostic biomarkers.

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Section: Methodsmentioning

confidence: 99%

Selective release of circRNAs in platelet‐derived extracellular vesicles

Preußer

Hung

Schneider

et al. 2018

J of Extracellular Vesicle

196

145

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“…HCV utilizes many receptors in vitro, including the low-density lipoprotein receptor ( Dreux et al, 2012;Feng et al, 2013;Ramakrishnaiah et al, 2013).…”

Section: Life Cyclementioning

confidence: 99%

“…Supporting this hypothesis, HPgV RNA-containing microvesicles positive for an exosomal marker (cellular CD63) were able to deliver viral RNA to uninfected PBMCs and viral RNA replicated within these cells ex vivo (Chivero et al, 2014). Other viruses such as hepatitis A virus and HCV have also been shown to utilize exosomes for viral transmission and intercellular communication (Bukong et al, 2014;Dreux et al, 2012;Feng et al, 2013;Ramakrishnaiah et al, 2013).…”

Section: Life Cyclementioning

confidence: 99%

Tropism of human pegivirus (formerly known as GB virus C/hepatitis G virus) and host immunomodulation: insights into a highly successful viral infection

Chivero

Stapleton

2015

Journal of General Virology

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Human pegivirus (HPgV; originally called GB virus C/hepatitis G virus) is an RNA virus within the genus Pegivirus of the family Flaviviridae that commonly causes persistent infection. Worldwide, 750 million people are actively infected (viraemic) and an estimated 0.75-1.5 billion people have evidence of prior HPgV infection. No causal association between HPgV and disease has been identified; however, several studies described a beneficial relationship between persistent HPgV infection and survival in individuals infected with human immunodeficiency virus. The beneficial effect appeared to be related to a reduction in host immune activation. HPgV replicates well in vivo (mean plasma viral loads typically .1¾10 7 genome copies ml -1 ); however, the virus grows poorly in vitro and systems to study this virus are limited. Consequently, mechanisms of viral persistence and host immune modulation remain poorly characterized, and the primary permissive cell type (s) has not yet been identified. HPgV RNA is found in liver, spleen, bone marrow and PBMCs, including Tand B-lymphocytes, NK-cells, and monocytes, although the mechanism of cell-to-cell transmission is unclear. HPgV RNA is also present in serum microvesicles with properties of exosomes. These microvesicles are able to transmit viral RNA to PBMCs in vitro, resulting in productive infection. This review summarizes existing data on HPgV cellular tropism and the effect of HPgV on immune activation in various PBMCs, and discusses how this may influence viral persistence. We conclude that an increased understanding of HPgV replication and immune modulation may provide insights into persistent RNA viral infection of humans. IntroductionHuman pegivirus (HPgV) is an RNA virus within the Pegivirus A species and family Flaviviridae (Adams et al., 2013;Stapleton et al., 2012a). The virus was originally called hepatitis G virus (HGV)/GB virus type C (GBV-C). The letters 'GB' represented the initials of a surgeon with acute hepatitis whose sera caused hepatitis in marmosets (Deinhardt et al., 1967). Subsequent studies found that this virus did not cause hepatitis and there was no direct evidence that the surgeon ('G. B.') was infected with HPgV. Thus, the virus (HGV/GBV-C), along with several related primate and bat viruses (GBV-A, GBV-C czp , GBV-D), was assigned to a new genus (Pegivirus) and renamed as HPgV (Adams et al., 2013;Stapleton et al., 2012a). HPgV has a 9.4 kb positive-sense ssRNA genome that is organized similarly to hepatitis C virus (HCV) (Fig. 1). HPgV and HCV are unusual amongst RNA viruses in that they commonly cause persistent infection in immune-competent humans.Although HPgV is not as efficient at establishing persistent infection as HCV, an estimated 25 % of infections persist and the other 75 % clear viraemia within 2 years of infection (Gutierrez et al., 1997;Tanaka et al., 1998a). The prevalence of HPgV viraemia in cross-sectional serum surveys of healthy blood donors in developed countries is between 1 and 5 %, whilst up to 20 % of blood donors in ...

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“…28 Exosome-mediated transmission of human viruses have been reported. 30,31 Could it also be the case for plant viruses, despite the presence of a thick surrounding cell wall that would act as a barrier for virus movement? Vesicular transport across the cell wall has been demonstrated in fungi.…”

Section: Change Of Paradigm?mentioning

confidence: 99%