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Antiviral Effects of Human Immunodeficiency Virus Type 1-specific Small Interfering RNAs Against Targets Conserved in Select Neurotropic Viral Strains

Overview
Journal J Virol
Date 2004 Nov 27
PMID 15564478
Citations 22
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Abstract

RNA interference, a natural biological phenomenon mediated by small interfering RNAs (siRNAs), has been demonstrated in recent studies to be an effective strategy against human immunodeficiency virus type 1 (HIV-1). In the present study, we used 21-bp chemically synthesized siRNA duplexes whose sequences were derived from the gp41 gene, nef, tat, and rev regions of viral RNA. These sequences are conserved in select neurotropic strains of HIV-1 (JR-FL, JR-CSF, and YU-2). The designed siRNAs exerted a potent antiviral effect on these HIV-1 strains. The antiviral effect was mediated at the RNA level (as observed by the down-regulation of the HIV-1-specific spliced transcript generating a 1.2-kbp reverse transcription [RT]-PCR product) as well as viral assembly on the cell membrane. Spliced transcripts (apart from the most abundant transcript generating a 1.2-kbp RT-PCR product) arising from an unspliced precursor likely contributed, albeit to a lesser extent, to the antiviral effect. The resultant progeny viruses had infectivities similar to that of input virus. We therefore conclude that these siRNAs interfere with the processing of the unspliced transcripts for the gp41 gene, tat, rev, and nef, eventually affecting viral assembly and leading to the overall inhibition of viral production. Apart from using the gp41 gene as a target, the conservation of each of these targets in the above-mentioned viral strains, as well as several primary isolates, would enable these siRNAs to be used as potent antiviral tools for investigations with cells derived from the central nervous system in order to evaluate their therapeutic potential and assess their utility in inhibiting HIV-1 neuropathogenesis and neuroinvasion.

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References
1.
Smit T, Wang B, Ng T, Osborne R, Brew B, Saksena N . Varied tropism of HIV-1 isolates derived from different regions of adult brain cortex discriminate between patients with and without AIDS dementia complex (ADC): evidence for neurotropic HIV variants. Virology. 2001; 279(2):509-26. DOI: 10.1006/viro.2000.0681. View

2.
Elbashir S, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T . Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature. 2001; 411(6836):494-8. DOI: 10.1038/35078107. View

3.
Myslinski E, Ame J, Krol A, Carbon P . An unusually compact external promoter for RNA polymerase III transcription of the human H1RNA gene. Nucleic Acids Res. 2001; 29(12):2502-9. PMC: 55750. DOI: 10.1093/nar/29.12.2502. View

4.
Glass W, Liu M, Kuziel W, Lane T . Reduced macrophage infiltration and demyelination in mice lacking the chemokine receptor CCR5 following infection with a neurotropic coronavirus. Virology. 2001; 288(1):8-17. PMC: 7142305. DOI: 10.1006/viro.2001.1050. View

5.
Brummelkamp T, Bernards R, Agami R . A system for stable expression of short interfering RNAs in mammalian cells. Science. 2002; 296(5567):550-3. DOI: 10.1126/science.1068999. View