Lately, several studies have shown the crucial role of Nef protein in viral replication and infection through the transformation of resting bystander CD4+ T cells to HIV-1 susceptible cells [111,186,190] while HIV-1 Gag protein plays a role in HIV-1 assembly and egress through the interaction with the exosomal membrane tetraspanins, CD81 and CD63 [110,158,191,192]. The gene discussed is CD4; the disease is infection.