Format

Send to

Choose Destination
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.

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.

PMID:
29765018
PMCID:
PMC5954121
DOI:
10.1038/s41467-018-04217-5
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center