Modulating HIV-1 RNA processing and utilization

Abstract

Expression of the integrated HIV-1 provirus is achieved by overcoming multiple barriers to the processing, transport and utilization of the viral RNA. Some of the strategies involve viral encoded proteins (i.e. Rev, Gag). However, in large part it is host factors that play essential roles in the movement of HIV-1 RNA from the site of transcription to its ultimate encapsidation into new virions. Identifying these factors and their mechanism of action provides not only important insights into HIV-1 molecular biology but also that of the cell machinery itself. In this review, we highlight the viral and host factors regulating the splicing, polyadenylation, transport, and translation of HIV-1 RNA. The observations made underline the multiple fate decisions that must be made at each stage of the viral RNA metabolic pathway and highlight potential new avenues for controlling HIV-1 replication.

In vitro and in vivo cleavage of HIV-1 RNA by new SOFA-HDV ribozymes and their potential to inhibit viral replication

“…sébastien Lainé, 1,2,4,6 Robert J. scarborough, 1,2 Dominique Lévesque, 5 Ludovic Didierlaurent, 6 Kaitlin J. soye, 1,2, † Marylène Mougel, 6 Jean-pierre perreault 5 and Anne Gatignol 1-3, Inhibiting gene expression to affect viral replication can be achieved by RNA-based methods including molecular decoys, antisense RNAs, ribozymes (RNA enzymes; Rzs) and small interfering (si) RNAs. [7][8][9] Rzs are catalytic RNAs that can be designed to specifically base-pair with and cleave an RNA target in trans.…”

“…Rev and cellular factors work in concert to bring these RNAs to the cytoplasm for translation. 6 RNA-based compounds are promising agents to inactivate viruses. New specific hepatitis delta virus (hDV)-derived ribozymes are natural molecules that can be engineered to specifically target a viral RNA.…”

HIV-1 RRE RNA acts as an RNA silencing suppressor by competing with TRBP-bound siRNAs

“…[38][39][40] The RRE-Rev interaction is critical in enabling the export of unspliced and singly spliced RNAs from the nucleus through the interaction with proteins involved in nuclear export. 41,42 Its complex secondary structure makes it probable that RRE may interact with other RNA-binding proteins. In addition, the RRE sequence is very well conserved across different lentiviruses.…”

The Regulation of HIV-1 mRNA Biogenesis

“…To date, 4 exonic splicing silencers (ESS), 1 intronic splicing silencer (ISS), 1 intronic splicing enhancer (ISE) and 6 splicing exonic enhancers (ESE) have been identified (Fig. 3B) (Exline, et al, 2008, McLaren, et al, 2008, Schaub, et al, 2007. Several SR proteins (SC35, SF2, SRp40, 9G8) have been shown to bind the viral splicing enhancers and regulate splicing, while members of the hnRNP A/B (A1, A2 and A3) family have been shown to inhibit the usage of viral splice sites by binding viral spicing silencer elements and counteracting the activity of SR proteins (McLaren, et al, 2008).…”

“…3B) (Exline, et al, 2008, McLaren, et al, 2008, Schaub, et al, 2007. Several SR proteins (SC35, SF2, SRp40, 9G8) have been shown to bind the viral splicing enhancers and regulate splicing, while members of the hnRNP A/B (A1, A2 and A3) family have been shown to inhibit the usage of viral splice sites by binding viral spicing silencer elements and counteracting the activity of SR proteins (McLaren, et al, 2008). A third group of proteins interacts with both, enhancer and silencer sequences, is the hnRNP H family (H', F, 2H9 and GRSF1).…”