CD39 represents a marker of T-cell exhaustion that is predominantly observed in chronic viral infections, such as HIV and hepatitis B. The expression of CD39 on CD4+ T cells leads to a higher tendency to apoptosis; lower function of Fox+ regulatory T cells; and, by reducing the release of IL-21, also a lower activation of B cells, which limits T-cell functions in the acute phase of viral infections [29]. This evidence concerns the gene CD4 and viral infectious disease.