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Updated: May 16, 2026
Peptide-based Identification of Functional Motifs and their Binding Partners
Published on: June 30, 2013
Characterization of rare lens epithelium-derived growth factor/p75 genetic variants identified in HIV-1 long-term
Rik Schrijvers1, Jonas Demeulemeester, Jan De Rijck
1Molecular Virology and Gene Therapy, KU Leuven, Leuven, Flanders, Belgium.
Objective:
Lens epithelium-derived growth factor (LEDGF)/p75 is a cellular binding partner of HIV-1 integrase and a crucial cofactor for HIV-1 replication. Here, we study two LEDGF/p75 exonic variants I436S and T473I, identified in HIV-1 long-term nonprogressors, together with Q472L.
Methods:
In-vitro binding assays, cell culture complementation, and functional rescue.
Results:
Binding affinities of wild-type, I436S, T473I, and Q472L LEDGF/p75 for HIV-1 integrase were comparable. All LEDGF/p75 variants bound equally well to LEDGF/p75 interacting partners JPO2 and PogZ. In addition, HIV-1 replication was evaluated in human somatic LEDGF/p75-knockout cells and LEDGF/p75-knockdown cells complemented with either wild-type LEDGF/p75 or the respective LEDGF/p75 variants. All variants rescued HIV-1 replication to wild-type levels, whereas LEDGF/p75 D366N, defective for interaction with HIV-1 integrase, did not.
Conclusion:
Although identified in a cohort of long-term nonprogressors, our study did not indicate that the I436S or T473I mutation in LEDGF/p75 affects the interaction with HIV-1 integrase.
