Human immunodeficiency virus type 1 messenger RNA (HIV-1 mRNA) (HIV-1 mRNA)

Human immunodeficiency virus type 1 (HIV-1) messenger RNA (mRNA) is the essential intermediary between the integrated viral DNA provirus and the production of viral proteins and new virions (Karn & Stoltzfus, 2012, Cold Spring Harb Perspect Med). Following transcription by host RNA polymerase II, the HIV-1 primary transcript undergoes complex alternative splicing to generate unspliced, singly spliced, and multiply spliced mRNA species (Watts et al., 2009, Nature). These transcripts are responsible for encoding all viral structural, enzymatic, and accessory proteins, while the unspliced 9.2 kb transcript also serves as the viral genome for packaging into new particles. In the context of HIV-1 infection, the persistence of viral mRNA synthesis despite antiretroviral therapy (ART) is a key marker of the viral reservoir and ongoing low-level replication (Rossi, 2006, Nature). Therapeutic targeting of HIV-1 mRNA involves the use of antisense oligonucleotides, RNA interference (RNAi), and ribozymes designed to bind specific, highly conserved sequences to induce RNA degradation or block translation (Amado et al., 2004, Hum Gene Ther). Furthermore, small molecule inhibitors are being explored to target structured RNA motifs like the Trans-activation Response (TAR) element and the Rev Response Element (RRE), which are critical for viral trans-activation and nuclear export of unspliced transcripts (Levine et al., 2006, PNAS).

Other names

HIV-1 RNAHIV-1 transcriptsHIV-1 genomic RNAHIV-1 proviral RNA

Antisense-mediated RNase H cleavage, RNA interference (RNAi) via the RISC complex, ribozyme-catalyzed site-specific cleavage, and small molecule-mediated steric hindrance of RNA-protein interactions (Karn & Stoltzfus, 2012, Cold Spring Harb Perspect Med; Rossi, 2006, Nature).