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Rare HIV-1 transmitted/founder lineages identified by deep viral sequencing contribute to rapid shifts in dominant quasispecies during acute and early infection.
- Source :
-
PLoS pathogens [PLoS Pathog] 2017 Jul 31; Vol. 13 (7), pp. e1006510. Date of Electronic Publication: 2017 Jul 31 (Print Publication: 2017). - Publication Year :
- 2017
-
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.
- Subjects :
- Adolescent
Adult
Cohort Studies
Female
HIV Infections immunology
HIV Infections transmission
HIV-1 classification
HIV-1 physiology
High-Throughput Nucleotide Sequencing
Humans
Immune Evasion
Male
Middle Aged
T-Lymphocytes, Cytotoxic immunology
T-Lymphocytes, Cytotoxic virology
Young Adult
HIV Infections virology
HIV-1 genetics
HIV-1 isolation & purification
Subjects
Details
- Language :
- English
- ISSN :
- 1553-7374
- Volume :
- 13
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- PLoS pathogens
- Publication Type :
- Academic Journal
- Accession number :
- 28759651
- Full Text :
- https://doi.org/10.1371/journal.ppat.1006510