dc.contributor | Yu Y. | |
dc.contributor | Scheel T.K.H. | |
dc.contributor | Luna J.M. | |
dc.contributor | Chung H. | |
dc.contributor | Nishiuchi E. | |
dc.contributor | Scull M.A. | |
dc.contributor | Echeverría Chagas Natalia, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares | |
dc.contributor | Ricardo-Lax I. | |
dc.contributor | Kapoor A. | |
dc.contributor | Lipkin I.W. | |
dc.contributor | Divers T.J. | |
dc.contributor | Antczak D.F. | |
dc.contributor | Tennant B.C. | |
dc.contributor | Rice C.M. | |
dc.creator | Yu, Y. | |
dc.creator | Scheel, T. K. H. | |
dc.creator | Luna, J. M. | |
dc.creator | Chung, H. | |
dc.creator | Nishiuchi, E. | |
dc.creator | Scull, M. A. | |
dc.creator | Echeverría Chagas, Natalia | |
dc.creator | Ricardo-Lax, I. | |
dc.creator | Kapoor, A. | |
dc.creator | Lipkin, I. W. | |
dc.creator | Divers, T. J. | |
dc.creator | Antczak, D. F. | |
dc.creator | Tennant, B. C. | |
dc.creator | Rice, C. M. | |
dc.date.accessioned | 2019-12-11T15:45:43Z | |
dc.date.accessioned | 2022-10-28T19:57:28Z | |
dc.date.available | 2019-12-11T15:45:43Z | |
dc.date.available | 2022-10-28T19:57:28Z | |
dc.date.created | 2019-12-11T15:45:43Z | |
dc.date.issued | 2017 | |
dc.identifier | 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 | |
dc.identifier | 1553-7366 | |
dc.identifier | https://hdl.handle.net/20.500.12008/22739 | |
dc.identifier | 10.1371/journal.ppat.1006694 | |
dc.identifier.uri | https://repositorioslatinoamericanos.uchile.cl/handle/2250/4976899 | |
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. | |
dc.language | en | |
dc.publisher | PLoS | |
dc.relation | PLoS Pathogens, 2017, 13 (10), art. no. e1006694 | |
dc.rights | Licencia Creative Commons Atribución (CC - By 4.0) | |
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) | |
dc.subject | MicroRNAs | |
dc.subject | Carcinoma Hepatocellular | |
dc.subject | HCC tissues | |
dc.title | miRNA independent hepacivirus variants suggest a strong evolutionary pressure to maintain miR-122 dependence | |
dc.type | Artículo | |