RNA structures facilitate recombination-mediated gene swapping in HIV-1.
Résumé
Many viruses, including retroviruses, undergo frequent recombination: a process which can increase their rate of adaptive evolution. In the case of HIV, recombination has been responsible for the generation of numerous inter-subtype recombinant variants with epidemiological importance in the AIDS pandemic. Although it is known that fragments of genetic material do not combine randomly during the generation of recombinant viruses, the mechanisms that lead to preferential recombination at specific sites are not fully understood. Here we reanalyze recent independent data defining (i) the structure of a complete HIV-1 RNA genome and (ii) favorable sites for recombination. We show that, in the absence of selection acting on recombinant genomes, regions harboring RNA structures in the NL4-3 model strain are strongly predictive of recombination breakpoints in the HIV-1 env gene of primary isolates. In addition, we find that breakpoints within recombinant HIV-1 genomes sampled from human populations, which have been extensively acted upon by natural selection, also co-localize with RNA structures. Critically, junctions between genes are both enriched in structured RNA elements and are also preferred sites for generating functional recombinant forms. These data suggest that RNA-structure-mediated recombination allows the virus to exchange intact genes rather than arbitrary sub-gene fragments, which is likely to increase the overall viability, and replication success, of the recombinant HIV progeny.