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Updated: Jun 22, 2026
Assessing the Innate Sensing of HIV-1 Infected CD4+ T Cells by Plasmacytoid Dendritic Cells Using an Ex vivo Co-culture System.
Published on: September 1, 2015
HIV integration site distributions in resting and activated CD4+ T cells infected in culture
Troy Brady1, Luis M Agosto, Nirav Malani
1Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Insights
HIV integration differs between resting and activated T cells. Activated cells favor gene-rich areas, potentially impacting latent reservoir formation and viral gene expression.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- Understanding HIV integration site selection is crucial for understanding latent reservoir formation.
- T cell activation status may influence where HIV integrates in the host genome.
Purpose of the Study:
- To determine if the location of human immunodeficiency virus (HIV) integration differs between resting and activated CD4 T cells.
- To investigate how integration site selection might contribute to the establishment of latent HIV reservoirs.
Main Methods:
- Primary resting or activated CD4 T cells were infected with HIV.
- Genomic locations of integrated provirus were determined using linker-mediated PCR and 454 sequencing.
- 2661 HIV integration sites were analyzed and compared to random distributions.
Main Results:
- HIV integration occurred in active transcription units in both resting and activated T cells.
- Integration sites in activated cells were enriched in gene-dense regions, CpG islands, and G/C-rich areas.
- Integration sites in activated cells showed stronger correlation with histone methylation patterns of active genes.
Conclusions:
- HIV integration site distribution shows significant differences between resting and activated CD4 T cells.
- Integration in resting T cells occurs in regions potentially less conducive to proviral gene expression.
- These findings suggest integration targeting influences latent reservoir dynamics.
Objective:
The goal of this study was to investigate whether the location of HIV integration differs in resting versus activated T cells, a feature that could contribute to the formation of latent viral reservoirs via effects on integration targeting.
Design:
Primary resting or activated CD4 T cells were infected with purified X4-tropic HIV in the presence and absence of nucleoside triphosphates and genomic locations of integrated provirus determined.
Methods:
We sequenced and analyzed a total of 2661 HIV integration sites using linker-mediated PCR and 454 sequencing. Integration site data sets were then compared to each other and to computationally generated random distributions.
Results:
HIV integration was favored in active transcription units in both cell types, but integration sites from activated cells were found more often in genomic regions that were dense in genes, dense in CpG islands, and enriched in G/C bases. Integration sites from activated cells were also more strongly correlated with histone methylation patterns associated with active genes.
Conclusion:
These data indicate that integration site distributions show modest but significant differences between resting and activated CD4 T cells, and that integration in resting cells occurs more often in regions that may be suboptimal for proviral gene expression.
