Nat Commun. 2018 May 15;9(1):1928. doi: 10.1038/s41467-018-04217-5.

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

Song H^1,², Giorgi EE³, Ganusov VV⁴, Cai F¹, Athreya G⁵, Yoon H³, Carja O⁶, Hora B¹, Hraber P³, Romero-Severson E³, Jiang C^1,⁷, Li X¹, Wang S⁸, Li H⁸, Salazar-Gonzalez JF^9,¹⁰, Salazar MG⁹, Goonetilleke N¹¹, Keele BF¹², Montefiori DC¹, Cohen MS¹¹, Shaw GM^8,¹³, Hahn BH^8,¹³, McMichael AJ¹⁴, Haynes BF¹, Korber B³, Bhattacharya T^3,¹⁵, Gao F^16,¹⁷.

Author information

1: Duke Human Vaccine Institute and Department of Medicine, Duke University Medical Center, Durham, NC, 27710, USA.
2: United States Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, 20910, USA.
3: Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM, 87544, USA.
4: Department of Microbiology, University of Tennessee, Knoxville, TN, 37996, USA.
5: Office for Research & Discovery, University of Arizona, Tucson, AZ, 85721, USA.
6: Department of Biology, University of Pennsylvania, Philadelphia, PA, 19104, USA.
7: National Engineering Laboratory For AIDS Vaccine, College of Life Science, Jilin University, Changchun, Jilin, 130012, China.
8: Department of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
9: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
10: MRC/UVRI and LSHTM Uganda Research Unit, Plot 51-57, Nakiwogo Road, Entebbe, Uganda.
11: Departments of Microbiology and Immunology & Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
12: AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, USA.
13: Department of Microbiology, University of Pennsylvania, Philadelphia, PA, 19104, USA.
14: Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK.
15: Santa Fe Institute, Santa Fe, NM, 87501, USA.
16: Duke Human Vaccine Institute and Department of Medicine, Duke University Medical Center, Durham, NC, 27710, USA. fgao@duke.edu.
17: National Engineering Laboratory For AIDS Vaccine, College of Life Science, Jilin University, Changchun, Jilin, 130012, China. fgao@duke.edu.

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.