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Viral reservoir characteristics in lymphoid tissues of HIV-1 elite controllers
Samantha K. Marzi, Chloé M. Naasz, Leah Carrere, Carmen Gasca Capote, Isabelle C. Roseto, Ce Gao, Matthias Cavassini, Andrea Mastrangelo, Mathias Lichterfeld, Matthieu Perreau, Xu G. Yu
Samantha K. Marzi, Chloé M. Naasz, Leah Carrere, Carmen Gasca Capote, Isabelle C. Roseto, Ce Gao, Matthias Cavassini, Andrea Mastrangelo, Mathias Lichterfeld, Matthieu Perreau, Xu G. Yu
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Research Article AIDS/HIV Infectious disease Virology

Viral reservoir characteristics in lymphoid tissues of HIV-1 elite controllers

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Abstract

Elite controllers (ECs) maintain undetectable levels of plasma viremia in the absence of treatment, but small reservoirs of replication-competent proviruses persist in the vast majority of these persons. We longitudinally studied paired blood and inguinal lymph node samples (LNMC) from 2 ECs to better characterize distinguishing features of viral reservoir cell dynamics in ECs. In both participants, we observed a 7- to 10-fold lower frequency of intact proviruses in LNMC samples relative to reservoir cells circulating in blood. The landscape of intact proviruses in both tissue compartments was dominated by shared large clones that were frequently integrated in noncoding DNA regions, but the frequency and diversity of intact proviruses was more limited in LNMCs. Of note, over 9–10 years of longitudinal follow-up, a 3- to 18-fold reduction of intact proviruses was observed. Together, these data support the hypothesis that viral reservoirs in EC blood and lymphoid tissues are under strong, likely immune-mediated selection pressure.

Authors

Samantha K. Marzi, Chloé M. Naasz, Leah Carrere, Carmen Gasca Capote, Isabelle C. Roseto, Ce Gao, Matthias Cavassini, Andrea Mastrangelo, Mathias Lichterfeld, Matthieu Perreau, Xu G. Yu

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Figure 2

Quantification of the proviral reservoirs.

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Quantification of the proviral reservoirs.
(A and C) Relative frequencie...
(A and C) Relative frequencies of intact and defective HIV-1 proviral sequences per million cells in PBMC and LNMC samples of Participant 1 (A) and Participant 2 (C) across time points. “Dx” denotes diagnosis. Horizontal bars indicate calculated fold changes between sample types. (B and D) Percentages of intact and defective HIV-1 proviral sequences out of the total number of proviral sequences detected in PBMC and LNMC samples of Participant 1 (B) and Participant 2 (D) across time points.

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