title: Deep sequencing of virus-infected cells reveals HIV-encoded small RNAs.
abstract: Small virus-derived interfering RNAs (viRNAs) play an important role in antiviral defence in plants, insects and nematodes by triggering the RNA interference (RNAi) pathway. The role of RNAi as an antiviral defence mechanism in mammalian cells has been obscure due to the lack of viRNA detection. Although viRNAs from different mammalian viruses have recently been identified, their functions and possible impact on viral replication remain unknown. To identify viRNAs derived from HIV-1, we used the extremely sensitive SOLiD(TM) 3 Plus System to analyse viRNA accumulation in HIV-1-infected T lymphocytes. We detected numerous small RNAs that correspond to the HIV-1 RNA genome. The majority of these sequences have a positive polarity (98.1%) and could be derived from miRNAs encoded by structured segments of the HIV-1 RNA genome (vmiRNAs). A small portion of the viRNAs is of negative polarity and most of them are encoded within the 3'-UTR, which may represent viral siRNAs (vsiRNAs). The identified vsiRNAs can potently repress HIV-1 production, whereas suppression of the vsiRNAs by antagomirs stimulate virus production. These results suggest that HIV-1 triggers the production of vsiRNAs and vmiRNAs to modulate cellular and/or viral gene expression.
authors.affiliation: Laboratory of Experimental Virology, Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ, The Netherlands.
authors.forename: Nick C T
authors.initials: NC
authors.lastname: Schopman
authors.forename: Marcel
authors.initials: M
authors.lastname: Willemsen
authors.forename: Ying Poi
authors.initials: YP
authors.lastname: Liu
authors.forename: Ted
authors.initials: T
authors.lastname: Bradley
authors.forename: Antoine
authors.initials: A
authors.lastname: van Kampen
authors.forename: Frank
authors.initials: F
authors.lastname: Baas
authors.forename: Ben
authors.initials: B
authors.lastname: Berkhout
authors.forename: Joost
authors.initials: J
authors.lastname: Haasnoot
mesh_terms: D001483:Base Sequence; D002478:Cells, Cultured; D015497:HIV-1 / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D034622:RNA Interference; D016372:RNA, Antisense / Q000737:chemistry; D034741:RNA, Small Interfering / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012357:RNA, Transfer, Lys / Q000737:chemistry; D012367:RNA, Viral / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017423:Sequence Analysis, RNA
chemical_list: D035683:MicroRNAs; D016372:RNA, Antisense; D034741:RNA, Small Interfering; D012357:RNA, Transfer, Lys; D012367:RNA, Viral