Section 61
Chapter 60,171

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

Kijak, G.H.; Sanders-Buell, E.; Chenine, A-Laurence.; Eller, M.A.; Goonetilleke, N.; Thomas, R.; Leviyang, S.; Harbolick, E.A.; Bose, M.; Pham, P.; Oropeza, C.; Poltavee, K.; O'Sullivan, A.Marie.; Billings, E.; Merbah, M.; Costanzo, M.C.; Warren, J.A.; Slike, B.; Li, H.; Peachman, K.K.; Fischer, W.; Gao, F.; Cicala, C.; Arthos, J.; Eller, L.A.; O'Connell, R.J.; Sinei, S.; Maganga, L.; Kibuuka, H.; Nitayaphan, S.; Rao, M.; Marovich, M.A.; Krebs, S.J.; Rolland, M.; Korber, B.T.; Shaw, G.

Plos Pathogens 13(7): E1006510


ISSN/ISBN: 1553-7366
PMID: 28759651
DOI: 10.1371/journal.ppat.1006510
Accession: 060170790

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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.

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