Our experiments revealed that symptomatic WNV+ donors exhibited higher frequencies of Tim-3+ and Tim-3+PD-1+ T cells compared to asymptomatic WNV+ donors throughout the course of infection, and Tim-3+ populations phenotypically were CD28+ CD57− naïve/differentiating and CD28− CD57− differentiated CD4+ and CD8+ T cells. Here, CD28 is linked to infection.