Rare HIV-1 transmitted/founder lineages identified by deep viral sequencing contribute to rapid shifts in dominant quasispecies during acute and early infection.
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.
Kijak, GH; Sanders-Buell, E; Chenine, A-L; Eller, MA; Goonetilleke, N; Thomas, R; Leviyang, S; Harbolick, EA; Bose, M; Pham, P; Oropeza, C; Poltavee, K; O'Sullivan, AM; Billings, E; Merbah, M; Costanzo, MC; Warren, JA; Slike, B; Li, H; Peachman, KK; Fischer, W; Gao, F; Cicala, C; Arthos, J; Eller, LA; O'Connell, RJ; Sinei, S; Maganga, L; Kibuuka, H; Nitayaphan, S; Rao, M; Marovich, MA; Krebs, SJ; Rolland, M; Korber, BT; Shaw, GM; Michael, NL; Robb, ML; Tovanabutra, S; Kim, JH
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