The three main goals of this work were: i) to demonstrate that CIB1 and CIB2 play a role in HIV-1 replication not only in cell lines but also in human CD4+ T-lymphocytes, the most abundant natural target cells; ii) comprehensively evaluate the potential role of CIB proteins throughout the HIV-1 replication cycle, in order to identify the step(s) impaired by the downregulation of CIB1 and CIB2 expression; and iii) begin to characterize the mechanisms through which CIB proteins promote HIV-1 infection. The gene discussed is CD4; the disease is HIV-1 infection.