HIV-1 Integration Sites in CD4+ T Cells During Primary, Chronic, and Late Presentation of HIV-1 Infection

Overview

Journal JCI Insight

Specialties Biomedical Engineering
General Medicine

Date 2021 Mar 30

PMID 33784259

Citations 7

Authors

Yik Lim Kok

Valentina Vongrad

Sandra E Chaudron

Mohaned Shilaih

Christine Leemann

Kathrin Neumann

Katharina Kusejko

Francesca Di Giallonardo

Herbert Kuster

Dominique L Braun

Roger D Kouyos

Huldrych F Gunthard

Karin J Metzner

Affiliations

Soon will be listed here.

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.

Citing Articles

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