1. HIV-1 integration sites in CD4+ T cells during primary, chronic, and late presentation of HIV-1 infection.
- Author
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Kok YL, Vongrad V, Chaudron SE, Shilaih M, Leemann C, Neumann K, Kusejko K, Di Giallonardo F, Kuster H, Braun DL, Kouyos RD, Günthard HF, and Metzner KJ
- Subjects
- Antiretroviral Therapy, Highly Active, Disease Progression, HIV Infections drug therapy, HIV Infections metabolism, HIV-1 metabolism, Humans, Lymphocyte Activation, Viral Load, CD4-Positive T-Lymphocytes metabolism, Cell Proliferation genetics, HIV Infections genetics, HIV-1 genetics, Host Microbial Interactions genetics, Neoplasms genetics, Virus Integration genetics, Virus Latency genetics
- 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.
- Published
- 2021
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