Derivation of primary sequences and secondary structures of rev responsive element from HIV-1 infected mothers and infants following vertical transmission.

We have characterized the primary RRE sequences of HIV-1, including in vivo genetic variation and functional motifs required for Rev-RRE interactions as well as evaluated the RNA secondary structures of RRE derived from five mother-infant pairs following vertical transmission. Multiple (157) RRE sequences derived from mother-infant pairs showed that primary nucleotide sequences of RRE were highly conserved with a low degree of viral heterogeneity following vertical transmission. We found that the RRE sequences from mothers and infants folded and retained all the essential stem-loop formation required for Rev-RRE interactions. More importantly, a primary 9-nucleotide (5'-CACTATGGG-3') RRE sequence in the stem-loop B that is required for optimal Rev recognition and must be presented as a stem-bulge-stem structure was highly conserved in most of the sequences. The domains required for RRE-host protein interactions were also conserved in most of the RRE sequences. Taken together, the primary RRE sequences in the context of secondary structures were maintained and the Rev-RRE interaction domains were conserved following vertical transmission, which is consistent with a crucial role of RRE in HIV-1 pathogenesis.