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

2018; Nature Portfolio; Volume: 9; Issue: 1 Linguagem: Inglês

10.1038/s41467-018-04217-5

2041-1723

Hongshuo Song, Elena E. Giorgi, Vitaly V. Ganusov, Fangping Cai, Gayathri S. Athreya, Hyejin Yoon, Oana Carja, Bhavna Hora, Peter Hraber, Ethan Romero-Severson, Chunlai Jiang, Xiaojun Li, Shuyi Wang, Hui Li, Jesus F. Salazar-Gonzalez, Maria G. Salazar, Nilu Goonetilleke, Brandon F. Keele, David C. Montefiori, Myron S. Cohen, George M. Shaw, Beatrice H. Hahn, Andrew J. McMichael, Barton F. Haynes, Bette Korber, Tanmoy Bhattacharya, Feng Gao,

HIV/AIDS drug development and treatment

Abstract 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.