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.