Ahluwalia, Jasmine K

Brahmachari, Samir K

Gupta, Ankit

Hariharan, Manoj

Khan, Sohrab Zafar

Lalwani, Mukesh

Mitra, Debashis

Pillai, Beena

Rawat, Pratima

Scaria, Vinod

Soni, Kartik

Retrovirology

English

PubMed

Background: Cellular miRNAs play an important role in the regulation of gene expression in eukaryotes. Recently, miRNAs have also been shown to be able to target and inhibit viral gene expression. Computational predictions revealed earlier that the HIV-1 genome includes regions that may be potentially targeted by human miRNAs. Here we report the functionality of predicted miR-29a target site in the HIV-1 nef gene.
Results: We find that the human miRNAs hsa-miR-29a and 29b are expressed in human peripheral blood mononuclear cells. Expression of a luciferase reporter bearing the nef miR-29a target site was decreased compared to the luciferase construct without the target site. Locked nucleic acid modified anti-miRNAs targeted against hsa-miR-29a and 29b specifically reversed the inhibitory effect mediated by cellular miRNAs on the target site. Ectopic expression of the miRNA results in repression of the target Nef protein and reduction of virus levels.
Conclusion: Our results show that the cellular miRNA hsa-miR29a downregulates the expression of Nef protein and interferes with HIV-1 replication.</p

Ahluwalia, JK

Khan, S

Soni, K

Rawat, P

Gupta, A

Hariharan, M

Scaria, V

Lalwani, M

Pillai, B

Mitra, D

Brahmachari, SK

Oxford University Research Archive (ORA)

Human cellular microRNA hsa-miR-29a interferes with viral nef protein expression and HIV-1 replication

Jasmine K Ahluwalia

Sohrab Khan

Kartik Soni

Pratima Rawat

Ankit Gupta

Manoj Hariharan

Vinod Scaria

Mukesh Lalwani

Beena Pillai

Debashis Mitra

Samir K Brahmachari

Springer - Publisher Connector

Background: Cellular miRNAs play an important role in the regulation of gene expression in eukaryotes. Recently, miRNAs have also been shown to be able to target and inhibit viral gene expression. Computational predictions revealed earlier that the HIV-1 genome includes regions that may be potentially targeted by human miRNAs. Here we report the functionality of predicted miR-29a target site in the HIV-1 nef gene. Results: We find that the human miRNAs hsa-miR-29a and 29b are expressed in human peripheral blood mononuclear cells. Expression of a luciferase reporter bearing the nef miR-29a target site was decreased compared to the luciferase construct without the target site. Locked nucleic acid modified anti-miRNAs targeted against hsa-miR-29a and 29b specifically reversed the inhibitory effect mediated by cellular miRNAs on the target site. Ectopic expression of the miRNA results in repression of the target Nef protein and reduction of virus levels. Conclusion: Our results show that the cellular miRNA hsa-miR29a downregulates the expression of Nef protein and interferes with HIV-1 replication

Oxford University Research Archive

BR: Inhibition of HIV-1 progeny virion release by cell-surface CD4 is relieved by expression of the viral Nef protein. Curr Biol

Brahmachari SK: Host-virus interaction: a new role for microRNAs. Retrovirology

Calin GA: Regulatory mechanisms of microRNAs involvement in cancer. Expert Opin Biol Ther

DZ: MicroRNAs in skeletal and cardiac muscle development.

Filipowicz W: Repression of protein synthesis by miRNAs: how many mechanisms? Trends Cell Biol

Fujii YR: Regulation of human immunodeficiency virus 1 transcription by nef microRNA.

Hatzigeorgiou A: A combined computationalexperimental approach predicts human microRNA targets. Genes Dev

Heat shock protein 40 is necessary for human immunodeficiency virus-1 Nef-mediated enhancement of viral gene expression and replication.

Ho WZ: Cellular microRNA expression correlates with susceptibility of monocytes/macrophages to HIV-1 infection. Blood

Human immunodeficiency virus-1 Nef protein interacts with Tat and enhances HIV-1 gene expression. FEBS Lett

Human MicroRNA targets. PLoS Biol

Hypersusceptibility to vesicular stomatitis virus infection in Dicer1-deficient mice is due to impaired miR24 and miR93 expression. Immunity

Increased virus replication in mammalian cells by blocking intracellular innate defense responses. Gene Ther

Interferon modulation of cellular microRNAs as an antiviral mechanism. Nature

Jeang KT: Insights into cellular microRNAs and human immunodeficiency virus type 1 (HIV-1).

Jeang KT: Small non-coding RNAs, mammalian cells, and viruses: regulatory interactions? Retrovirology

JT: A hexanucleotide element directs microRNA nuclear import. Science

Kim VN: Processing of intronic microRNAs.

MicroInspector: a web tool for detection of miRNA binding sites in an RNA sequence. Nucleic Acids Res

MJ: Pathogenicity and immunogenicity of attenuated, nef-deleted HIV-1 strains in vivo. Retrovirology

Moelling K: Dicer is involved in protection against influenza A virus infection.

Mouse microRNA profiles determined with a new and sensitive cloning method. Nucleic Acids Res

Nef: &quot;necessary and enforcing factor&quot;

Plasterk RH: Targeted inhibition of miRNA maturation with morpholinos reveals a role for miR-375 in pancreatic islet development. PLoS Biol

Positive and negative modulation of viral and cellular mRNAs by liver-specific microRNA miR-122. Cold Spring Harb Symp Quant Biol

Rehmsmeier M: RNAhybrid: microRNA target prediction easy, fast and flexible. Nucleic Acids Res

S: Perspectives on chemistry and therapeutic applications of Locked Nucleic Acid (LNA). Chem Rev

Sarnow P: Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science

SK: Host-virus genome interactions: macro roles for microRNAs. Cell Microbiol

SK: Targets for human encoded microRNAs in HIV genes.

The MicroRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing. Mol Cell

Voinnet O: A cellular microRNA mediates antiviral defense in human cells. Science

YR: HIV-1 nef suppression by virally encoded microRNA. Retrovirology

Zhang H: Cellular microRNAs contribute to HIV-1 latency in resting primary CD4(+) T lymphocytes. Nat Med

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Human cellular microRNA hsa-miR-29a interferes with viral nef protein expression and HIV-1 replication

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Oxford University Research Archive (ORA)

Springer - Publisher Connector

Oxford University Research Archive