Title:Targeting Virus-host Interactions of HIV Replication
VOLUME: 16 ISSUE: 10
Author(s):Caroline Weydert, Jan De Rijck, Frauke Christ and Zeger Debyser
Affiliation:Laboratory for Molecular Virology and Gene Therapy, Department for Pharmaceutical and Pharmacological Sciences, KU Leuven, Kapucijnenvoer 33 VCTB+5, Leuven, Flanders, Belgium.
Keywords:HIV, Cofactors, APOBEC3G, Antivirals, LEDGF/p75, LEDGIN, P-TEFb.
Abstract:Cellular proteins that are hijacked by HIV in order to complete its replication cycle, form
attractive new targets for antiretroviral therapy. In particular, the protein-protein interactions between
these cellular proteins (cofactors) and viral proteins are of great interest to develop new therapies. Research
efforts have led to the validation of different cofactors and some successes in therapeutic applications.
Maraviroc, the first cofactor inhibitor approved for human medicinal use, provided a proof of
concept. Furthermore, compounds developed as Integrase-LEDGF/p75 interaction inhibitors (LEDGINs)
have advanced to early clinical trials. Other compounds targeting cofactors and cofactor-viral
protein interactions are currently under development. Likewise, interactions between cellular restriction factors and their
counteracting HIV protein might serve as interesting targets in order to impair HIV replication. In this respect, compounds
targeting the Vif-APOBEC3G interaction have been described. In this review, we focus on compounds targeting the Integrase-
LEDGF/p75 interaction, the Tat-P-TEFb interaction and the Vif-APOBEC3G interaction. Additionally we give an
overview of currently discovered compounds presumably targeting cellular cofactor-HIV protein interactions.
