| A selex-screened aptamer of human hepatitis b virus rna encapsidation signal suppresses viral replication | |
| Feng, Hui1; Beck, Juergen2; Nassal, Michael2; Hu, Kang-hong1 | |
| 刊名 | Plos one
 |
| 2011-11-18 | |
| 卷号 | 6期号:11页码:10 |
| ISSN号 | 1932-6203 |
| DOI | 10.1371/journal.pone.0027862 |
| 通讯作者 | Feng, hui() |
| 英文摘要 | Background: the specific interaction between hepatitis b virus (hbv) polymerase (p protein) and the e rna stem-loop on pregenomic (pg) rna is crucial for viral replication. it triggers both pgrna packaging and reverse transcription and thus represents an attractive antiviral target. rna decoys mimicking e in p protein binding but not supporting replication might represent novel hbv inhibitors. however, because generation of recombinant enzymatically active hbv polymerase is notoriously difficult, such decoys have as yet not been identified. methodology/principal findings: here we used a selex approach, based on a new in vitro reconstitution system exploiting a recombinant truncated hbv p protein (minip), to identify potential e decoys in two large e rna pools with randomized upper stem. selection of strongly p protein binding rnas correlated with an unexpected strong enrichment of a residues. two aptamers, s6 and s9, displayed particularly high affinity and specificity for minip in vitro, yet did not support viral replication when part of a complete hbv genome. introducing s9 rna into transiently hbv producing hepg2 cells strongly suppressed pgrna packaging and dna synthesis, indicating the s9 rna can indeed act as an e decoy that competitively inhibits p protein binding to the authentic e signal on pgrna. conclusions/significance: this study demonstrates the first successful identification of human hbv e aptamers by an in vitro selex approach. effective suppression of hbv replication by the s9 aptamer provides proof-of-principle for the ability of e decoy rnas to interfere with viral p-e complex formation and suggests that s9-like rnas may further be developed into useful therapeutics against chronic hepatitis b. |
| WOS关键词 | HEPADNAVIRUS REVERSE-TRANSCRIPTASE ; STEM-LOOP STRUCTURE ; IN-VITRO ; DNA-SYNTHESIS ; TERMINAL PROTEIN ; CELL-LINE ; POLYMERASE ; BINDING ; ACTIVATION ; INITIATION |
| WOS研究方向 | Science & Technology - Other Topics |
| WOS类目 | Multidisciplinary Sciences |
| 语种 | 英语 |
| 出版者 | PUBLIC LIBRARY SCIENCE |
| WOS记录号 | WOS:000297789200033 |
| 内容类型 | 期刊论文 |
| URI标识 | http://www.corc.org.cn/handle/1471x/2375897 |
| 专题 | 武汉病毒研究所 |
| 通讯作者 | Feng, Hui |
| 作者单位 | 1.Chinese Acad Sci, Wuhan Inst Virol, State Key Lab Virol, Wuhan, Peoples R China 2.Univ Hosp Freiburg, Freiburg, Germany |
| 推荐引用方式 GB/T 7714 | Feng, Hui,Beck, Juergen,Nassal, Michael,et al. A selex-screened aptamer of human hepatitis b virus rna encapsidation signal suppresses viral replication[J]. Plos one,2011,6(11):10. |
| APA | Feng, Hui,Beck, Juergen,Nassal, Michael,&Hu, Kang-hong.(2011).A selex-screened aptamer of human hepatitis b virus rna encapsidation signal suppresses viral replication.Plos one,6(11),10. |
| MLA | Feng, Hui,et al."A selex-screened aptamer of human hepatitis b virus rna encapsidation signal suppresses viral replication".Plos one 6.11(2011):10. |
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