Song, HS; Giorgi, EE; Ganusov, VV; Cai, FP; Athreya, G; Yoon, H; Carja, O; Hora, B; Hraber, P; Romero-Severson, E; Jiang, CL; Li, XJ; Wang, SY; 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.