3 years ago

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

Hui Li, Meera Bose, Agnes-Laurence Chenine, Melanie Merbah, Anne Marie O’Sullivan, Sorachai Nitayaphan, Elizabeth A. Harbolick, Shelly J. Krebs, Jerome H. Kim, Margaret C. Costanzo, Michael A. Eller, Gustavo H. Kijak, Bette T. Korber, Phuc Pham, Eric Sanders-Buell, Mangala Rao, Merlin L. Robb, Lucas Maganga, Robert J. O’Connell, Erik Billings, Rasmi Thomas, Nilu Goonetilleke, Sodsai Tovanabutra, Mary A. Marovich, Nelson L. Michael, Morgane Rolland, Feng Gao, Claudia Cicala, Celina Oropeza, Leigh A. Eller, Samuel Sinei, Joanna A. Warren, Bonnie Slike, Sivan Leviyang, Hannah Kibuuka, Kultida Poltavee, George M. Shaw, James Arthos, Will Fischer, Kristina K. Peachman

by Gustavo H. Kijak, Eric Sanders-Buell, Agnes-Laurence Chenine, Michael A. Eller, Nilu Goonetilleke, Rasmi Thomas, Sivan Leviyang, Elizabeth A. Harbolick, Meera Bose, Phuc Pham, Celina Oropeza, Kultida Poltavee, Anne Marie O’Sullivan, Erik Billings, Melanie Merbah, Margaret C. Costanzo, Joanna A. Warren, Bonnie Slike, Hui Li, Kristina K. Peachman, Will Fischer, Feng Gao, Claudia Cicala, James Arthos, Leigh A. Eller, Robert J. O’Connell, Samuel Sinei, Lucas Maganga, Hannah Kibuuka, Sorachai Nitayaphan, Mangala Rao, Mary A. Marovich, Shelly J. Krebs, Morgane Rolland, Bette T. Korber, George M. Shaw, Nelson L. Michael, Merlin L. Robb, Sodsai Tovanabutra, Jerome H. Kim

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.

Publisher URL: http://journals.plos.org/plosone/article

DOI: 10.1371/journal.ppat.1006510

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