In progressive lentiviral infections (i.e., SIV infection of macaques and HIV infection of humans), the majority of gut CD4+ T cells are initially killed by direct viral cytopathic effects due to ongoing viral replication, which drives apoptosis of epithelial enterocytes, immune activation in the gut, recruitment of innate immune cells and inflammation, leading to further damage of the gut epithelium fueling mucosal barrier destruction and microbial translocation that trigger chronic systemic immune activation and inflammation [66,68,108]. This evidence concerns the gene CD4 and HIV infectious disease.