By using a Y2H screen with human cDNA libraries, p115-RhoGEF, an activator of Rho GTPase, was found to interact with the gp41 CT through its C-terminal regulatory domain [128] . The gp41 mutants that lost the ability to bind p115 showed impaired replication kinetics in T-cell lines such as SupT1, H9, and Jurkat, suggesting that the gp41 CT could modulate the activity of p115-RhoGEF to support virus replication [128] .