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| Content Provider | PubMed Central |
|---|---|
| Author | Bukong, Terence N. Momen-heravi, Fatemeh Karen, Kodys Bala, Shashi Szabo, Gyongyi |
| Editor | Luo, Guangxiang |
| Copyright Year | 2014 |
| Abstract | Antibodies targeting receptor-mediated entry of HCV into hepatocytes confer limited therapeutic benefits. Evidence suggests that exosomes can transfer genetic materials between cells; however, their role in HCV infection remains obscure. Here, we show that exosomes isolated from sera of chronic HCV infected patients or supernatants of J6/JFH1-HCV-infected Huh7.5 cells contained HCV RNA. These exosomes could mediate viral receptor-independent transmission of HCV to hepatocytes. Negative sense HCV RNA, indicative of replication competent viral RNA, was present in exosomes of all HCV infected treatment non-responders and some treatment-naïve individuals. Remarkably, HCV RNA was associated with Ago2, HSP90 and miR-122 in exosomes isolated from HCV-infected individuals or HCV-infected Huh7.5 cell supernatants. Exosome-loading with a miR-122 inhibitor, or inhibition of HSP90, vacuolar H+-ATPases, and proton pumps, significantly suppressed exosome-mediated HCV transmission to naïve cells. Our findings provide mechanistic evidence for HCV transmission by blood-derived exosomes and highlight potential therapeutic strategies. |
| Related Links | http://dx.doi.org/10.1371/journal.ppat.1004424 |
| Starting Page | 1004424 |
| File Format | |
| ISSN | 15537374 |
| e-ISSN | 15537374 |
| Journal | PLoS Pathogens |
| Issue Number | 10 |
| Volume Number | 10 |
| Language | English |
| Publisher | Public Library of Science |
| Publisher Date | 2014-10-01 |
| Access Restriction | Open |
| Rights Holder | Public Library of Science |
| Subject Keyword | Immunology Genetics Molecular Biology Microbiology Parasitology Virology Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics Virology Molecular Biology Parasitology Immunology Microbiology |
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