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HIV-1 integration sites in CD4+ T cells during primary, chronic, and late presentation of HIV-1 infection


Kok, Yik Lim; Vongrad, Valentina; Chaudron, Sandra E; Shilaih, Mohaned; Leemann, Christine; Neumann, Kathrin; Kusejko, Katharina; Di Giallonardo, Francesca; Kuster, Herbert; Braun, Dominique L; Kouyos, Roger D; Günthard, Huldrych F; Metzner, Karin J (2021). HIV-1 integration sites in CD4+ T cells during primary, chronic, and late presentation of HIV-1 infection. Journal of clinical investigation insight, 6(9):e143940.

Abstract

HIV-1 is capable of integrating its genome into that of its host cell. We examined the influence of the activation state of CD4+ T cells, the effect of antiretroviral therapy (ART), and the clinical stage of HIV-1 infection on HIV-1 integration site features and selection. HIV-1 integration sites were sequenced from longitudinally sampled resting and activated CD4+ T cells from 12 HIV-1-infected individuals. In total, 589 unique HIV-1 integration sites were analyzed: 147, 391, and 51 during primary, chronic, and late presentation of HIV-1 infection, respectively. As early as during primary HIV-1 infection and independent of the activation state of CD4+ T cells collected on and off ART, HIV-1 integration sites were preferentially detected in recurrent integration genes, genes associated with clonal expansion of latently HIV-1-infected CD4+ T cells, cancer-related genes, and highly expressed genes. The preference for cancer-related genes was more pronounced at late stages of HIV-1 infection. Host genomic features of HIV-1 integration site selection remained stable during HIV-1 infection in both resting and activated CD4+ T cells. In summary, characteristic HIV-1 integration site features are preestablished as early as during primary HIV-1 infection and are found in both resting and activated CD4+ T cells.

Abstract

HIV-1 is capable of integrating its genome into that of its host cell. We examined the influence of the activation state of CD4+ T cells, the effect of antiretroviral therapy (ART), and the clinical stage of HIV-1 infection on HIV-1 integration site features and selection. HIV-1 integration sites were sequenced from longitudinally sampled resting and activated CD4+ T cells from 12 HIV-1-infected individuals. In total, 589 unique HIV-1 integration sites were analyzed: 147, 391, and 51 during primary, chronic, and late presentation of HIV-1 infection, respectively. As early as during primary HIV-1 infection and independent of the activation state of CD4+ T cells collected on and off ART, HIV-1 integration sites were preferentially detected in recurrent integration genes, genes associated with clonal expansion of latently HIV-1-infected CD4+ T cells, cancer-related genes, and highly expressed genes. The preference for cancer-related genes was more pronounced at late stages of HIV-1 infection. Host genomic features of HIV-1 integration site selection remained stable during HIV-1 infection in both resting and activated CD4+ T cells. In summary, characteristic HIV-1 integration site features are preestablished as early as during primary HIV-1 infection and are found in both resting and activated CD4+ T cells.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Infectious Diseases
04 Faculty of Medicine > Institute of Medical Virology
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > General Medicine
Language:English
Date:10 May 2021
Deposited On:11 Nov 2021 10:24
Last Modified:25 Feb 2024 02:48
Publisher:American Society for Clinical Investigation
ISSN:2379-3708
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1172/jci.insight.143940
PubMed ID:33784259
  • Content: Published Version
  • Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)