HIV-1 nef suppression by virally encoded microRNA

被引：198

作者：

Omoto S. ^{[1
]}

Ito M. ^{[1
,3
]}

Tsutsumi Y. ^{[4
]}

Ichikawa Y. ^{[2
]}

Okuyama H. ^{[2
]}

Brisibe E.A. ^{[5
]}

Saksena N.K. ^{[6
]}

Fujii Y.R. ^{[1
]}

机构：

[1] Molec. Biol./Retroviral Genet. Group, Grad. School of Pharmaceut. Sciences, Nagoya City University

[2] Division of Nutritional Sciences, Grad. School of Pharmaceut. Sciences, Nagoya City University

[3] Department of Molecular Diagnostics, Fields of Pathology, Nagoya Univ. Grad. School of Med.

[4] Department of Pathology, Fujita Health Univ. School of Med., Toyoake

[5] Res./Scientific Developments Div., Molecular Bio/Sciences Limited, Calabar, Cross River State

[6] Retroviral Genetics Division, Center for Virus Research, Westmead Millenium Institute, Westmead

来源：

Retrovirology | / 1卷 / 1期

关键词：

Long Terminal Repeat; Spinal Muscular Atrophy; Prototype Foamy Virus; Style Vector; Confocal Laser Microscopy Analysis;

D O I：

10.1186/1742-4690-1-44

中图分类号：

学科分类号：

摘要：

Background: 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. 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 (∼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. © 2004 Omoto et al; licensee BioMed Central Ltd.

引用

页数：12

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