Omoto Shinya, Ito Masafumi, Tsutsumi Yutaka, Ichikawa Yuko, Okuyama Harumi, Brisibe Ebiamadon Andi, Saksena Nitin K, Fujii Yoichi R
Molecular Biology and Retroviral Genetics Group, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, Japan.
Retrovirology. 2004 Dec 15;1:44. doi: 10.1186/1742-4690-1-44.
MicroRNAs (miRNAs) are 21 to approximately 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 (approximately 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.
微小RNA（miRNA）长度为21至约25个核苷酸（nt），并与mRNA相互作用，通过RNA干扰（RNAi）触发翻译抑制或RNA切割，这取决于与靶mRNA的互补程度。我们最近的研究表明，来自长期不进展者（LTNP）艾滋病患者的HIV-1 nef双链RNA（dsRNA）抑制了HIV-1的转录。
在这里，我们展示了在HIV-1持续感染细胞中产生nef衍生的miRNA的可能性。此外，与预测的nef miRNA（约25 nt，miR-N367）相对应的nef短发夹RNA（shRNA）可以在体外阻断HIV-1 Nef表达，并且shRNA/miR-N367的抑制作用可能与LTNP（15-2-2）中的低病毒血症有关。在15-2-2模型小鼠中，可能由nef导致的体重减轻也被对应于体内nef表达抑制的shRNA/miR-N367所抑制。
这些数据表明，在HIV-1感染细胞中产生的nef/U3 miRNA可能通过RNAi途径抑制Nef功能和HIV-1毒力。
