HIV-1: To Splice or Not to Splice, That Is the Question

The transcription of the HIV-1 provirus results in only one type transcript—full length genomic RNA. To make mRNA transcripts for accessory proteins Tat and Rev, RNA must completely splice. Vif, Vpr, Env undergo splicing but not completely. Genomic (which also functions as Gag Gag/Pro/Pol precursor polyproteins) splice at all. can tolerate a surprising range relative abundance individual transcript types, amount aberrant even odd splicing; however, it over-splice, which loss full-length has dramatic fitness cost. Cells typically do unspliced/incompletely spliced transcripts, so circumvent this cell policing mechanism to allow some while suppressing most. Splicing is controlled by secondary structure, cis-acting regulatory sequences bind factors, viral protein Rev. There still much work be done clarify combinatorial effects these regulators. These control mechanisms represent attractive targets induce over-splicing an antiviral strategy. Finally, been implicated latency, date there little supporting evidence such mechanism. In review we apply what known cellular understand HIV-1, present data from our newer more sensitive deep sequencing assays quantifying different types.