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.
HIV-1 integration sites in CD4+ T cells during primary, chronic, and late presentation of HIV-1 infection
Yik Lim Kok,Valentina Vongrad,Sandra E. Chaudron,Mohaned Shilaih,Christine Leemann,Kathrin Neumann,K. Kusejko,Francesca Di Giallonardo,H. Kuster,D. Braun,R. Kouyos,H. Günthard,K. Metzner
Published 2021 in JCI Insight
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- Publication year
2021
- Venue
JCI Insight
- Publication date
2021-03-30
- Fields of study
Medicine
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Semantic Scholar, PubMed
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