CD8A and HIV infectious disease: In untreated HIV infection, progressive functional impairment of CD8+ T cells is accompanied by the upregulation of “immune checkpoint markers” such as PD-1, CD160, 2B4, LAG-3, and TIGIT, (with negligible expression of TIM3 and CTLA-4), which can inhibit signaling downstream of the TCR on HIV-specific CD8+ T cells, and in chronic viral infections, promote apoptosis (39, 171, 187, 188).