IL-21 has been shown to enhance antiviral NK cell and CD8 T-cell immunity in animal models of non-HIV viral infections, and has been used successfully in safety trials of patients with advanced malignancy, thereby making it an attractive candidate for anti-HIV therapy.98 In SIV-infected macaques, IL-21 administration increased perforin and granzyme B expression in CD8, effector CD4, and NK cell subsets; however, it remains unknown whether these favorable quantitative changes will translate into improved antiviral function and elimination of latently infected cells. This evidence concerns the gene CD8A and viral infectious disease.