Title: Characterization of rare LEDGF/p75 genetic variants identified in HIV-1 long-term non-progressors
Authors: Schrijvers, Rik
Demeulemeester, Jonas
De Rijck, Jan
Christ, Frauke
GĂ©rard, Melanie
Debyser, Zeger ×
Gijsbers, Rik #
Issue Date: Feb-2013
Publisher: Gower Academic Journals
Series Title: AIDS vol:27 issue:4 pages:539-543
Abstract: OBJECTIVE:: LEDGF/p75 is a cellular binding partner of HIV-1 integrase and a crucial co-factor for HIV-1 replication. Here, we study two LEDGF/p75 exonic variants I436S and T473I, identified in HIV-1 long-term non-progressors, 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 non-progressors, our study did not indicate that the I436S or T473I mutation in LEDGF/p75 affects the interaction with HIV-1 integrase.
ISSN: 0269-9370
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Virology and Gene Therapy
× corresponding author
# (joint) last author

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