Rare HIV-1 transmitted/founder lineages identified by deep viral sequencing contribute to rapid shifts in dominant quasispecies during acute and early infection

PLoS Pathog. 2017 Jul 31;13(7):e1006510. doi: 10.1371/journal.ppat.1006510. eCollection 2017 Jul.

Abstract

In order to inform the rational design of HIV-1 preventive and cure interventions it is critical to understand the events occurring during acute HIV-1 infection (AHI). Using viral deep sequencing on six participants from the early capture acute infection RV217 cohort, we have studied HIV-1 evolution in plasma collected twice weekly during the first weeks following the advent of viremia. The analysis of infections established by multiple transmitted/founder (T/F) viruses revealed novel viral profiles that included: a) the low-level persistence of minor T/F variants, b) the rapid replacement of the major T/F by a minor T/F, and c) an initial expansion of the minor T/F followed by a quick collapse of the same minor T/F to low frequency. In most participants, cytotoxic T-lymphocyte (CTL) escape was first detected at the end of peak viremia downslope, proceeded at higher rates than previously measured in HIV-1 infection, and usually occurred through the exploration of multiple mutational pathways within an epitope. The rapid emergence of CTL escape variants suggests a strong and early CTL response. Minor T/F viral strains can contribute to rapid and varied profiles of HIV-1 quasispecies evolution during AHI. Overall, our results demonstrate that early, deep, and frequent sampling is needed to investigate viral/host interaction during AHI, which could help identify prerequisites for prevention and cure of HIV-1 infection.

MeSH terms

  • Adolescent
  • Adult
  • Cohort Studies
  • Female
  • HIV Infections / immunology
  • HIV Infections / transmission
  • HIV Infections / virology*
  • HIV-1 / classification
  • HIV-1 / genetics*
  • HIV-1 / isolation & purification*
  • HIV-1 / physiology
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Immune Evasion
  • Male
  • Middle Aged
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / virology
  • Young Adult