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

Hongshuo Song, Elena E. Giorgi, Vitaly V. Ganusov, Fangping Cai, Gayathri 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 and Feng Gao ()
Additional contact information
Hongshuo Song: Duke University Medical Center
Elena E. Giorgi: Los Alamos National Laboratory
Vitaly V. Ganusov: University of Tennessee
Fangping Cai: Duke University Medical Center
Gayathri Athreya: University of Arizona
Hyejin Yoon: Los Alamos National Laboratory
Oana Carja: University of Pennsylvania
Bhavna Hora: Duke University Medical Center
Peter Hraber: Los Alamos National Laboratory
Ethan Romero-Severson: Los Alamos National Laboratory
Chunlai Jiang: Duke University Medical Center
Xiaojun Li: Duke University Medical Center
Shuyi Wang: University of Pennsylvania
Hui Li: University of Pennsylvania
Jesus F. Salazar-Gonzalez: University of Alabama at Birmingham
Maria G. Salazar: University of Alabama at Birmingham
Nilu Goonetilleke: University of North Carolina at Chapel Hill
Brandon F. Keele: Frederick National Laboratory for Cancer Research
David C. Montefiori: Duke University Medical Center
Myron S. Cohen: University of North Carolina at Chapel Hill
George M. Shaw: University of Pennsylvania
Beatrice H. Hahn: University of Pennsylvania
Andrew J. McMichael: University of Oxford
Barton F. Haynes: Duke University Medical Center
Bette Korber: Los Alamos National Laboratory
Tanmoy Bhattacharya: Los Alamos National Laboratory
Feng Gao: Duke University Medical Center

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: 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.

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04217-5

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DOI: 10.1038/s41467-018-04217-5

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