Selective clonal persistence of human retroviruses in vivo: radial chromatin organization, integration site and host transcription

Abstract

The human retroviruses HTLV-1 and HIV-1 persist in vivo as a reservoir of latently infected T-cell clones. It is poorly understood what determines which clones survive in the reservoir. We compared >160,000 HTLV-1 integration sites (>40,000 HIV-1 sites) from T-cells isolated ex vivo from naturally-infected subjects with >230,000 HTLV-1 integration sites (>65,000 HIV-1 sites) from in vitro infection, to identify genomic features that determine selective clonal survival. Three statistically independent factors together explained >40% of the observed variance in HTLV-1 clonal survival in vivo: the radial intranuclear position of the provirus, its genomic distance from the centromere, and the intensity of local host genome transcription. The radial intranuclear position of the provirus and its distance from the centromere also explained ~7% of clonal persistence of HIV-1 in vivo. Selection for the intranuclear and intrachromosomal location of the provirus, and host transcription intensity, favours clonal persistence of human retroviruses in vivo.