AI Article Synopsis
- Different retroviruses, like HIV-1, have unique integration patterns that virologists have studied for over 20 years.
- Researchers discovered specific amino acids in the HIV-1 integrase that interact with target DNA, influencing where the virus integrates into the host genome.
- Certain natural variants of the integrase, which change the virus's integration preferences, are linked to faster disease progression and are influenced by the host's immune response and treatment options.
Article 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.
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| http://dx.doi.org/10.1016/j.chom.2014.09.016 | DOI Listing |
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