LEDGF/p75 and transportin-SR2 are cellular cofactors of HIV integrase and novel targets for antiviral therapy

The HIV replication cycle is an elaborate interplay between the viral machinery and cellular proteins. In this review we propose that protein-protein interactions between cellular proteins and HIV integrase are new targets for future antiviral therapy. We focus on the early steps of HIV replication, namely viral entry, uncoating, reverse transcription, trafficking, nuclear import and integration, and the host cell proteins involved herein. We then discuss the feasibility of developing small-molecule protein-protein interaction inhibitors as antiviral agents. Next, we review the HIV integrase cofactors described in the literature highlighting two validated cofactors, lens epitheliumderived growth factor/p75 and transportin-SR2, which are discussed in detail. Finally, a speculative viewpoint is given on small-molecule protein-protein interaction inhibitors as future HIV inhibitors. © 2009 Future Medicine Ltd.

Jaar van publicatie:2009

Toegankelijkheid:Open