In-depth single-cell analysis of translation-competent HIV-1 reservoirs identifies cellular sources of plasma viremia

Basiel Cole, Laurens Lambrechts, Pierre Gantner, Ytse Noppe, Noah Bonine, Wojciech Witkowski, Lennie Chen, Sarah Palmer, James I. Mullins, Nicolas Chomont, Marion Pardons and Linos Vandekerckhove ()
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Basiel Cole: Ghent University
Laurens Lambrechts: Ghent University
Pierre Gantner: Université de Montréal
Ytse Noppe: Ghent University
Noah Bonine: Ghent University
Wojciech Witkowski: Ghent University
Lennie Chen: University of Washington
Sarah Palmer: The University of Sydney
James I. Mullins: University of Washington
Nicolas Chomont: Université de Montréal
Marion Pardons: Ghent University
Linos Vandekerckhove: Ghent University

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: Abstract Clonal expansion of HIV-infected cells contributes to the long-term persistence of the HIV reservoir in ART-suppressed individuals. However, the contribution from cell clones that harbor inducible proviruses to plasma viremia is poorly understood. Here, we describe a single-cell approach to simultaneously sequence the TCR, integration sites and proviral genomes from translation-competent reservoir cells, called STIP-Seq. By applying this approach to blood samples from eight participants, we show that the translation-competent reservoir mainly consists of proviruses with short deletions at the 5’-end of the genome, often involving the major splice donor site. TCR and integration site sequencing reveal that cell clones with predicted pathogen-specificity can harbor inducible proviruses integrated into cancer-related genes. Furthermore, we find several matches between proviruses retrieved with STIP-Seq and plasma viruses obtained during ART and upon treatment interruption, suggesting that STIP-Seq can capture clones that are responsible for low-level viremia or viral rebound.

Date: 2021
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DOI: 10.1038/s41467-021-24080-1

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