Early pandemic HIV-1 integration site preferences differ across anatomical sites

Area of Science:

• Virology
• Genomics
• Molecular Biology

Background:

• Human immunodeficiency virus type 1 (HIV-1) establishes lifelong reservoirs through DNA integration.
• HIV-1 integration occurs across various tissues, but site characteristics by anatomical location remain largely uncharacterized.
• Early pandemic HIV-1 subtype B integration patterns across tissues are investigated.

Purpose of the Study:

• To investigate tissue-specific differences in HIV-1 integration site location and characteristics.
• To compare HIV-1 integration patterns across distinct anatomical sites in early HIV-1 infection.

Main Methods:

• Integration site analysis from matched tissue samples (esophagus, blood, stomach, duodenum, colon) and brain tissue.
• Evaluation of integration frequency near genomic features (genes, repetitive elements, DNA structures).
• Comparative analysis of integration patterns across tissues and individuals.

Main Results:

• HIV-1 integration site patterns significantly differ across tissues.
• Brain tissue shows reduced integration into genes and increased integration into repetitive and accessible DNA regions.
• Tissue-specific integration hotspots exist, with some shared across sites; genes linked to HIV-1 diseases are frequently targeted.

Conclusions:

• The tissue microenvironment shapes HIV-1 integration patterns.
• Tissue-specific integration site features contribute to HIV-1 persistence.
• Findings have implications for understanding HIV-1 disease progression and developing targeted therapies.