In-depth single-cell analysis of translation-competent HIV-1 reservoirs identifies cellular sources of plasma viremia.
Nat Commun
; 12(1): 3727, 2021 06 17.
Article
en En
| MEDLINE
| ID: mdl-34140517
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Viremia
/
Infecciones por VIH
/
VIH-1
/
Provirus
/
Antirretrovirales
/
Análisis de la Célula Individual
Límite:
Humans
/
Male
/
Middle aged
Idioma:
En
Año:
2021
Tipo del documento:
Article