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HIV-1 nef suppression by virally encoded microRNA
Shinya Omoto1, Masafumi Ito, Yutaka Tsutsumi
1Molecular Biology and Retroviral Genetics Group, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, Japan. shinyaomoto@hotmail.com
Background:
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.
Results:
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.
Conclusions:
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.