We have also observed an absolute requirement for CXCR4 signaling in HIV-1 latent infection of resting CD4 T cells [44] and demonstrated that HIV-1 relies on viral envelope and the Gαi-dependent signaling from CXCR4 to activate a cellular actin-depolymerizing factor, cofilin, to increase the cortical actin dynamics for viral intracellular migration [44]. This evidence concerns the gene CD4 and disease arising from reactivation of latent virus.