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Campo DC | Valor | Lengua/Idioma |
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dc.contributor.author | Yu, Y. | - |
dc.contributor.author | Scheel, T. K. H. | - |
dc.contributor.author | Luna, J. M. | - |
dc.contributor.author | Chung, H. | - |
dc.contributor.author | Nishiuchi, E. | - |
dc.contributor.author | Scull, M. A. | - |
dc.contributor.author | Echeverría Chagas, Natalia | - |
dc.contributor.author | Ricardo-Lax, I. | - |
dc.contributor.author | Kapoor, A. | - |
dc.contributor.author | Lipkin, I. W. | - |
dc.contributor.author | Divers, T. J. | - |
dc.contributor.author | Antczak, D. F. | - |
dc.contributor.author | Tennant, B. C. | - |
dc.contributor.author | Rice, C. M. | - |
dc.date.accessioned | 2019-12-11T15:45:43Z | - |
dc.date.available | 2019-12-11T15:45:43Z | - |
dc.date.issued | 2017 | - |
dc.identifier.citation | Yu, Y., Scheel, T., Luna J., y otros. "miRNA independent hepacivirus variants suggest a strong evolutionary pressure to maintain miR-122 dependence". PLoS Pathogens [en línea], 2017, 13 (10), art. no. e1006694. doi: 10.1371/journal.ppat.1006694 | es |
dc.identifier.issn | 1553-7366 | - |
dc.identifier.uri | https://hdl.handle.net/20.500.12008/22739 | - |
dc.description.abstract | Hepatitis C virus (HCV) requires the liver specific micro-RNA (miRNA), miR-122, to replicate. This was considered unique among RNA viruses until recent discoveries of HCV-related hepaciviruses prompting the question of a more general miR-122 dependence. Among hepaciviruses, the closest known HCV relative is the equine non-primate hepacivirus (NPHV). Here, we used Argonaute cross-linking immunoprecipitation (AGO-CLIP) to confirm AGO binding to the single predicted miR-122 site in the NPHV 5’UTR in vivo. To study miR-122 requirements in the absence of NPHV-permissive cell culture systems, we generated infectious NPHV/HCV chimeric viruses with the 5’ end of NPHV replacing orthologous HCV sequences. These chimeras were viable even in cells lacking miR-122, although miR-122 presence enhanced virus production. No other miRNAs bound this region. By random mutagenesis, we isolated HCV variants partially dependent on miR-122 as well as robustly replicating NPHV/HCV variants completely independent of any miRNAs. These miRNA independent variants even replicate and produce infectious particles in non-hepatic cells after exogenous delivery of apolipoprotein E (ApoE). Our findings suggest that miR-122 independent HCV and NPHV variants have arisen and been sampled during evolution, yet miR-122 dependence has prevailed. We propose that hepaciviruses may use this mechanism to guarantee liver tropism and exploit the tolerogenic liver environment to avoid clearance and promote chronicity. | es |
dc.format.extent | 21 h | es |
dc.format.mimetype | application/pdf | es |
dc.language.iso | en | es |
dc.publisher | PLoS | es |
dc.relation.ispartof | PLoS Pathogens, 2017, 13 (10), art. no. e1006694 | es |
dc.rights | Las obras depositadas en el Repositorio se rigen por la Ordenanza de los Derechos de la Propiedad Intelectual de la Universidad de la República.(Res. Nº 91 de C.D.C. de 8/III/1994 – D.O. 7/IV/1994) y por la Ordenanza del Repositorio Abierto de la Universidad de la República (Res. Nº 16 de C.D.C. de 07/10/2014) | es |
dc.subject | MicroRNAs | es |
dc.subject | Carcinoma Hepatocellular | es |
dc.subject | HCC tissues | es |
dc.title | miRNA independent hepacivirus variants suggest a strong evolutionary pressure to maintain miR-122 dependence | es |
dc.type | Artículo | es |
dc.contributor.filiacion | Yu Y. | - |
dc.contributor.filiacion | Scheel T.K.H. | - |
dc.contributor.filiacion | Luna J.M. | - |
dc.contributor.filiacion | Chung H. | - |
dc.contributor.filiacion | Nishiuchi E. | - |
dc.contributor.filiacion | Scull M.A. | - |
dc.contributor.filiacion | Echeverría Chagas Natalia, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares | - |
dc.contributor.filiacion | Ricardo-Lax I. | - |
dc.contributor.filiacion | Kapoor A. | - |
dc.contributor.filiacion | Lipkin I.W. | - |
dc.contributor.filiacion | Divers T.J. | - |
dc.contributor.filiacion | Antczak D.F. | - |
dc.contributor.filiacion | Tennant B.C. | - |
dc.contributor.filiacion | Rice C.M. | - |
dc.rights.licence | Licencia Creative Commons Atribución (CC - By 4.0) | es |
dc.identifier.doi | 10.1371/journal.ppat.1006694 | - |
Aparece en las colecciones: | Publicaciones académicas y científicas - Facultad de Ciencias |
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101371journalppat1006694.pdf | 4,04 MB | Adobe PDF | Visualizar/Abrir |
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