CD4 and infection: Vpr protein likely contributes to disease progression in HIV-1-infected patients in several ways: (1) by inhibiting the proliferation of T cells and inducing cellular differentiation [20,31,63]; (2) by enabling productive infection of primary macrophages and reactivating virus production from latency, which contributes to virus production in the absence of CD4+ T cells and to the establishment of drug resistant reservoirs in patients early in infection [4,6,7,18,64]; (3) by contributing to the bystander cell depletion in lymphoid tissues, peripheral blood, and the CNS [12,38,65].