HIV-1 integrase variants retarget viral integration and are associated with disease progression in a chronic infection cohort
Related Experiment Video
Updated: Apr 19, 2026

Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors
Published on: April 9, 2014
Jonas Demeulemeester1, Sofie Vets2, Rik Schrijvers2
1Laboratory for Molecular Virology and Gene Therapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven-University of Leuven, 3000 Leuven, Belgium; Laboratory for Biomolecular Modeling, Department of Chemistry, KU Leuven-University of Leuven, 3000 Leuven, Belgium.
Abstract:
Distinct integration patterns of different retroviruses, including HIV-1, have puzzled virologists for over 20 years. A tetramer of the viral integrase (IN) assembles on the two viral cDNA ends, docks onto the target DNA (tDNA), and catalyzes viral genome insertion into the host chromatin. We identified the amino acids in HIV-1 IN that directly contact tDNA bases and affect local integration site sequence selection. These residues also determine the propensity of the virus to integrate into flexible tDNA sequences. Remarkably, natural polymorphisms INS119G and INR231G retarget viral integration away from gene-dense regions. Precisely these variants were associated with rapid disease progression in a chronic HIV-1 subtype C infection cohort. These findings link integration site selection to virulence and viral evolution, but also to the host immune response and antiretroviral therapy, since HIV-1 IN119 is under selection by HLA alleles and integrase inhibitors.
More Related Videos
09:31Amplification, Next-generation Sequencing, and Genomic DNA Mapping of Retroviral Integration Sites
Published on: March 22, 2016
14:27CRISPR-Cas9-based Genome Engineering to Generate Jurkat Reporter Models for HIV-1 Infection with Selected Proviral Integration Sites
Published on: November 14, 2018
Related Concept Videos
Size and Structure of Viral Genomes
Retrovirus Life Cycles
Mechanisms of Retrovirus-induced Cancers
Retroviruses
Non-LTR Retrotransposons
Viral Mutations