Tracking HIV-1 recombination to resolve its contribution to HIV-1 evolution in natural infection.

Publication Date: 
Tuesday, May 15, 2018
Song H, Giorgi EE, Ganusov VV, Cai F, Athreya G, Yoon H, Carja O, Hora B, Hraber P, Romero-Severson E, Jiang C, Li X, Wang S, Li H, Salazar-Gonzalez JF, Salazar MG, Goonetilleke N, Keele BF, Montefiori DC, Cohen MS, Shaw GM, Hahn BH, McMichael AJ, Haynes BF, Korber B, Bhattacharya T, Gao F

Recombination in HIV-1 is well documented, but its importance in the low-diversity setting of within-host diversification is less understood. Here we develop a novel computational tool (RAPR (Recombination Analysis PRogram)) to enable a detailed view of in vivo viral recombination during early infection, and we apply it to near-full-length HIV-1 genome sequences from longitudinal samples. Recombinant genomes rapidly replace transmitted/founder (T/F) lineages, with a median half-time of 27 days, increasing the genetic complexity of the viral population. We identify recombination hot and cold spots that differ from those observed in inter-subtype recombinants. Furthermore, RAPR analysis of longitudinal samples from an individual with well-characterized neutralizing antibody responses shows that recombination helps carry forward resistance-conferring mutations in the diversifying quasispecies. These findings provide insight into molecular mechanisms by which viral recombination contributes to HIV-1 persistence and immunopathogenesis and have implications for studies of HIV transmission and evolution in vivo.

Nat Commun.