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

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Title: Selective clonal persistence of human retroviruses in vivo: radial chromatin organization, integration site and host transcription
Authors: Melamed, A
Fitzgerald, T
Wang, Y
Ma, J
Birney, E
Bangham, C
Item Type: Journal Article
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.
Issue Date: 29-Apr-2022
Date of Acceptance: 8-Mar-2022
URI: http://hdl.handle.net/10044/1/96102
DOI: 10.1126/sciadv.abm6210
ISSN: 2375-2548
Publisher: American Association for the Advancement of Science
Journal / Book Title: Science Advances
Volume: 8
Issue: 17
Copyright Statement: © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). This is an open-access article distributed under the terms of the Creative Commons Attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Sponsor/Funder: Wellcome Trust
Wellcome Trust
Funder's Grant Number: 207477
207477/Z/17/Z
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
HUMAN-CHROMOSOMES
DOMAIN ORGANIZATION
T-CELLS
GENOME
ARCHITECTURE
EXPANSION
NUCLEI
Publication Status: Published
Article Number: ARTN eabm6210
Appears in Collections:Department of Infectious Diseases
Faculty of Medicine



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