Working model for HPgV persistence. Clinical studies show HPgV to be associated with significantly reduced expression of the activation marker CD69 on NK cells, and activation markers CD38, CD69 and CD25 on CD4+ and CD8+ T cells. Thus, HPgV infection is associated with reduced immune cell activation. In addition, B cells usually do not mount an antibody response to HPgV proteins during viremia, though they develop E2 antibodies at the time of, or after clearance of viremia. Due to the impairment of both cellular and humoral immunity, HPgV replicates to titers typically greater than 1 × 107 genome copies/ml of plasma. In this study, NK cells expressed less interferon gamma following IL-12 stimulation, potentially contributing to dysfunctional immune regulation of CD8+ T cells.