Fig. 1

The HIV-1 antisense gene, asp. The figure shows a schematic representation of the HIV-1 proviral genome with structural and enzymatic genes (gag, pol, env), regulatory genes (tat and rev), and accessory genes (vif, vpr, vpu, nef) expressed from the proviral 5’ LTR. The antisense gene asp is expressed from a negative sense promoter in the U3 region of the 3’ LTR in a manner independent of the viral transactivator, Tat. The negative sense promoter contains binding sites for USF, Ets-1, LEF-1, Sp1 and NF-κB. The antisense transcript Ast is a bifunctional RNA with both noncoding and protein-coding activities. The former is carried out in the nucleus: Ast acts as a lncRNA that promotes epigenetic silencing of HIV-1 by recruiting the histone methyltransferase (PRC2) to the 5’ LTR leading to trimethylation of lysine 27 on histone H3 (H3K27me3), which leads to assembly of the nucleosome Nuc-1, and inhibition of transcription. In addition, Ast is translocated to the cytoplasm where it functions as a mRNA and leads to the expression of the antisense protein ASP. In non-productively infected cells, ASP accumulates in the nucleus, whereas in productively infected cells ASP localizes in the cytoplasm and on the cell membrane in close proximity of the ENV. Further, upon viral budding and release, ASP is also detectable on the viral envelope