| Autor: |
Cole, Basiel, Lambrechts, Laurens, Gantner, Pierre, Noppe, Ytse, Bonine, Noah, Witkowski, Wojciech, Chen, Lennie, Palmer, Sarah, Mullins, James I., Chomont, Nicolas, Pardons, Marion, Vandekerckhove, Linos |
| Předmět: |
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| Zdroj: |
Nature Communications; 6/17/2021, Vol. 12 Issue 1, p1-13, 13p |
| Abstrakt: |
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. To provide in depth characterization of HIV reservoir cells, the authors here develop a single-cell approach to simultaneously sequence TCR, integration sites and proviral genomes, called STIP-Seq, and show that the translation-competent reservoir mainly consists of proviruses with short deletions at the 5'-end of the genome. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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