Our contention is that local concentrations of ps20, in tissue such as the gut, may drive HIV-1 infection and CD4+ T cell loss by increasing adhesion antigen expression on CD4+ T cells through autocrine and paracrine effects, thereby highlighting a novel role for the ancient whey acidic protein, WFDC1/ps20, in HIV-1 pathogenesis. This evidence concerns the gene WFDC1 and HIV-1 infection.