(A) Functional requirement of the HIV RRE: Early in the viral lifecycle, fully spliced viral RNAs are exported from the nucleus in a Rev/RRE-independent manner. Among these, Rev mRNA are translated and Rev is imported into the nucleus. In the late phase of the lifecycle, nuclear RRE-containing RNAs recruit Rev and cellular nuclear-export machinery, allowing them to circumvent splicing and transit to the cytoplasm, where they are either translated or packaged into assembling virions (B) Organization of the 116 aa HIV-1 Rev and amino acid changes in the trans-dominant M10 variant. NLS; nuclear localization signal, NES, nuclear export signal. Pink areas flanking the NLS represent Rev oligomerization domains.