In this study, we demonstrate a significant impact of early R5-SHIV infection on critical aspects of T cell function at and beyond the 5-week time point of maximal CD4 T cell depletion and viral load, including upregulation of PD-1 expression, differential suppression of gp120-specific T cell responses and preferential accumulation of Treg cells in lymphoid tissues. The gene discussed is ITIH4; the disease is ring chromosome 5.