The slightly more moderate inhibitory effect of overexpressed Cul3 on HIV-1 infection, when compared to a depletion of Cul3 via siRNA, could be explained by the fact that endogenous protein levels of Cul3 in HEK293T cells are relatively high, which sets a high base level and hence restricts the dynamic range of an overexpression approach. The gene discussed is CUL3; the disease is HIV-1 infection.