HIV-1 nef suppression by virally encoded microRNA.
HIV-1 nef suppression by virally encoded microRNA.
复制标题
DOI：
10.1186/1742-4690-1-44
复制
发表时间：
2004-12-15
期刊：
影响因子：
3.3
通讯作者：
Fujii YR
中科院分区：
文献类型：
--
作者：
Omoto S;Ito M;Tsutsumi Y;Ichikawa Y;Okuyama H;Brisibe EA;Saksena NK;Fujii YR
微小RNA（microRNAs，miRNAs）长21~25个核苷酸（nt），与靶mRNA相互作用，根据与靶mRNA的互补程度，通过RNA干扰（RNA interference，RNAi）触发翻译抑制或RNA切割。我们最近的研究表明，HIV-1 nef dsRNA从艾滋病患者谁是长期非进展者（LTNP）抑制HIV-1的转录。在这里，我们展示了nef衍生的miRNAs在HIV-1持续感染的细胞中产生的可能性。此外，对应于预测的nef miRNA（~25 nt，miR-N367）的nef短发夹RNA（shRNA）可以在体外阻断HIV-1 Nef表达，并且shRNA/miR-N367的抑制将与LTNP中的低病毒血症相关（15-2-2）。在15-2-2模型小鼠中，可能由nef引起的体重减轻也被shRNA/miR-N367抑制，对应于体内nef表达的抑制。这些数据表明，HIV-1感染细胞中产生的nef/U3 miRNAs可能通过RNAi途径抑制Nef功能和HIV-1毒力。
MicroRNAs (miRNAs) are 21~25-nucleotides (nt) long and interact with mRNAs to trigger either translational repression or RNA cleavage through RNA interference (RNAi), depending on the degree of complementarity with the target mRNAs. Our recent study has shown that HIV-1 nef dsRNA from AIDS patients who are long-term non-progressors (LTNPs) inhibited the transcription of HIV-1. Here, we show the possibility that nef-derived miRNAs are produced in HIV-1 persistently infected cells. Furthermore, nef short hairpin RNA (shRNA) that corresponded to a predicted nef miRNA (~25 nt, miR-N367) can block HIV-1 Nef expression in vitro and the suppression by shRNA/miR-N367 would be related with low viremia in an LTNP (15-2-2). In the 15-2-2 model mice, the weight loss, which may be rendered by nef was also inhibited by shRNA/miR-N367 corresponding to suppression of nef expression in vivo. These data suggest that nef/U3 miRNAs produced in HIV-1-infected cells may suppress both Nef function and HIV-1 virulence through the RNAi pathway.