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miRNA independent hepacivirus variants suggest a strong evolutionary pressure to maintain miR-122 dependence.
Yu, Yingpu; Scheel, Troels K H; Luna, Joseph M; Chung, Hachung; Nishiuchi, Eiko; Scull, Margaret A; Echeverría, Natalia; Ricardo-Lax, Inna; Kapoor, Amit; Lipkin, W Ian; Divers, Thomas J; Antczak, Douglas F; Tennant, Bud C; Rice, Charles M.
Afiliación
  • Yu Y; Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY, United States of America.
  • Scheel TKH; Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY, United States of America.
  • Luna JM; Copenhagen Hepatitis C Program, Department of Infectious Diseases, Hvidovre Hospital, and Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Chung H; Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY, United States of America.
  • Nishiuchi E; Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY, United States of America.
  • Scull MA; Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY, United States of America.
  • Echeverría N; Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY, United States of America.
  • Ricardo-Lax I; Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY, United States of America.
  • Kapoor A; Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay.
  • Lipkin WI; Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY, United States of America.
  • Divers TJ; Department of Pediatrics, College of Medicine, The Ohio State University, Columbus, OH, United States of America.
  • Antczak DF; Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, OH, United States of America.
  • Tennant BC; Center for Infection and Immunity, Mailman School of Public Health and College of Physicians & Surgeons, Columbia University, New York, NY, United States of America.
  • Rice CM; Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States of America.
PLoS Pathog ; 13(10): e1006694, 2017 10.
Article en En | MEDLINE | ID: mdl-29084265
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Hepatitis C / Hepacivirus / Evolución Molecular / MicroARNs / Tropismo Viral Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: PLoS Pathog Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Hepatitis C / Hepacivirus / Evolución Molecular / MicroARNs / Tropismo Viral Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: PLoS Pathog Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos