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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Evolution, Molecular*
  • Genetic Variation
  • Genotype
  • HIV Infections / virology*
  • HIV-1 / classification
  • HIV-1 / genetics*
  • HIV-1 / isolation & purification
  • Humans
  • Longitudinal Studies
  • Male
  • Phylogeny
  • Recombination, Genetic*