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Updated: Aug 25, 2026
Amplification, Next-generation Sequencing, and Genomic DNA Mapping of Retroviral Integration Sites
Published on: March 22, 2016
Monocyte-derived macrophages exhibit distinct and more restricted HIV-1 integration site repertoire than CD4(+) T
Yik Lim Kok1,2, Valentina Vongrad1,2, Mohaned Shilaih1,2
1Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.
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.
Insights
Human immunodeficiency virus type 1 (HIV-1) integration targets distinct gene repertoires in macrophages versus CD4(+) T cells. Macrophage integration sites are more restricted, influencing viral latency and host genetics.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- The host genetic landscape influences human immunodeficiency virus type 1 (HIV-1) proviral fate.
- Studies on HIV-1 integration sites in macrophages are limited.
- Understanding integration patterns is crucial for HIV-1 persistence research.
Purpose of the Study:
- To investigate and compare HIV-1 integration site patterns in monocyte-derived macrophages (MDMs) and activated CD4(+) T cells.
- To analyze the genomic distribution and genetic features of integration sites.
- To explore the impact of HIV-1 integrase polymorphisms on integration specificity.
Main Methods:
- Analysis of 1,484 unique HIV-1 integration sites in MDMs and CD4(+) T cells from ART-treated individuals.
- Ex vivo infection with autologous HIV-1 during the acute phase.
- Comparison of integration site distribution, genetic features, and nucleotide selection specificity.
Main Results:
- HIV-1 integration site distribution and genetic features were similar between MDMs and CD4(+) T cells.
- Gene cluster overlap for HIV-1 hosting was higher in MDMs.
- Frequencies of integration in HIV-1-interacting protein genes differed between cell types.
- HIV-1-hosting genes associated with CD4(+) T cell clonal expansion were enriched in CD4(+) T cell hotspots, but not MDM hotspots.
Conclusions:
- The gene repertoire targeted by HIV-1 in MDMs is distinct and more restricted compared to CD4(+) T cells.
- Cell-type-specific integration patterns may influence HIV-1 latency and persistence.
- Host genetics play a role in shaping the HIV-1 reservoir in different immune cells.
