Viral RNA species produced within HIV-1-infected cells and phases of HIV-1 RNA expression. (A) Viral RNA species produced within HIV-1-infected cells. HIV-1 genes are shown relative to the long terminal repeats (LTR). The viral genomic or 9-kb unspliced RNA shows the location of 5′ (D) and 3′ (A) splice sites. The incompletely and multiply spliced HIV-1 viral RNAs (4-kb and 2-kb size classes) are shown as black boxes. Spliced RNAs are denoted by the translated open reading frames and by the exon content. (Figure is adapted from ; reproduced, with permission, from American Society for Microbiology © 2008.) (B) Early and late phases of HIV-1 RNA expression. Full-length unspliced 9-kb RNA, incompletely spliced 4-kb RNA, and multiply spliced 2-kb RNA species are constitutively expressed in the nucleus. In the absence of Rev (upper panel), or when the concentration of Rev is below the threshold necessary for function, the 9-kb and 4-kb transcripts are excluded from the cytoplasm and either spliced or degraded. In contrast, the fully processed 2-kb RNA are constitutively exported to the cytoplasm and used to express Rev, Tat, and Nef. When the levels of Rev in the nucleus are sufficiently high (lower panel), the nuclear export of 9-kb and 4-kb RNAs is activated and the translation of all viral proteins ensues. (Ball and stick) The Rev response element. (Figure adapted from ; reproduced, with permission, from Annual Review of Microbiology © 1998).