In addition, landmark studies in LCMV (67) and then SIV/HIV-1 infection (33, 34, 62, 171, 172) highlighted the relevance of multiple ICs co-expression (i.e., CD160, 2B4, TIM-3, T cell immunoreceptor with Ig and ITIM domains-TIGIT, CTLA-4 and LAG-3) to define deeply exhausted virus-specific CD8 T cells. This evidence concerns the gene CD8A and HIV-1 infection.