[HTML][HTML] Monocyte-derived macrophages exhibit distinct and more restricted HIV-1 integration site repertoire than CD4+ T cells

YL Kok, V Vongrad, M Shilaih, F Di Giallonardo… - Scientific reports, 2016 - nature.com
Scientific reports, 2016nature.com
The host genetic landscape surrounding integrated HIV-1 has an impact on the fate of the
provirus. Studies analysing HIV-1 integration sites in macrophages are scarce. We studied
HIV-1 integration site patterns in monocyte-derived macrophages (MDMs) and activated
CD4+ T cells derived from seven antiretroviral therapy (ART)-treated HIV-1-infected
individuals whose cells were infected ex vivo with autologous HIV-1 isolated during the
acute phase of infection. A total of 1,484 unique HIV-1 integration sites were analysed. Their …
Abstract
The host genetic landscape surrounding integrated HIV-1 has an impact on the fate of the provirus. Studies analysing HIV-1 integration sites in macrophages are scarce. We studied HIV-1 integration site patterns in monocyte-derived macrophages (MDMs) and activated CD4+ T cells derived from seven antiretroviral therapy (ART)-treated HIV-1-infected individuals whose cells were infected ex vivo with autologous HIV-1 isolated during the acute phase of infection. A total of 1,484 unique HIV-1 integration sites were analysed. Their distribution in the human genome and genetic features, and the effects of HIV-1 integrase polymorphisms on the nucleotide selection specificity at these sites were indistinguishable between the two cell types, and among HIV-1 isolates. However, the repertoires of HIV-1-hosting gene clusters overlapped to a higher extent in MDMs than in CD4+ T cells. The frequencies of HIV-1 integration events in genes encoding HIV-1-interacting proteins were also different between the two cell types. Lastly, HIV-1-hosting genes linked to clonal expansion of latently HIV-1-infected CD4+ T cells were over-represented in gene hotspots identified in CD4+ T cells but not in those identified in MDMs. Taken together, the repertoire of genes targeted by HIV-1 in MDMs is distinct from and more restricted than that of CD4+ T cells.
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