HIV-1 integrase variants retarget viral integration and are associated with disease progression in a chronic infection cohort.

ABSTRACT: Distinct integration patterns of different retroviruses have puzzled virologists for over 20 years. The viral integrase (IN), as part of the intasome complex, docks onto the target DNA (tDNA) and catalyzes the insertion of the viral genome into the host chromatin. We identified retroviral IN amino acids directly contacting tDNA bases and affecting the local integration site sequence biases. 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, without affecting the interaction with the lentiviral tethering cofactor LEDGF/p75 (PSIP1). Precisely these variants were associated with rapid disease progression in a chronic HIV-1 subtype C i

ORGANISM(S): Homo sapiens

SUBMITTER: Jonas Demeulemeester 

PROVIDER: E-GEOD-61003 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress