HIV-1 nef suppression by virally encoded microRNA

Shinya Omoto,Nitin K Saksena,Yutaka Tsutsumi,Ebiamadon Brisibe,Yuko Ichikawa,Masafumi Ito,Yoichi R Fujii,Harumi Okuyama

doi:10.1186/1742-4690-1-44

Abstract

BackgroundMicroRNAs (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.ResultsHere, 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.ConclusionsThese 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.

Highlights

MicroRNAs are 21~25-nucleotides 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
The results presented here show that nef short hairpin RNAs corresponding to the nef miRNAs efficiently block RNA stability or mRNA translation, perhaps an indication that human immunodeficiency virus (HIV)-1 regulates its own replication by using nef miRNAs
During the preliminary stages of this study, our curiosity was fixed on the need to find out if there was any relationship between nef miRNAs and HIV-1-infected cells

Summary

Results

We show the possibility that nef-derived miRNAs are produced in HIV-1 persistently infected cells. 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 inhibited by shRNA/ miR-N367 corresponding to suppression of nef expression in vivo

Background

Results and Discussion

Materials and Methods