Individuals with CCR5Delta32 mutant genotype can naturally resist human immunodeficiency virus type 1(HIV-1) infection. The mechanism is mainly due to CCR5Delta32 mutant protein expressed in the individual peripheral blood mononuclear cells (PBMCs), through trans-dominant negative (TDN) effect, which can inhibit two types of HIV-1 coreceptor (CCR5 and CXCR4) on the cell surface from producing. The recombinant lentiviruses, namely Lenti-CCR5Delta32, were generated and used to infect human PBMCs. HIV-1 infection of the PBMCs transduced with Lenti-CCR5Delta32 showed that CCR5Delta32 protein expressed in human PBMCs was able to inhibit R5, X4, and R5X4 HIV-1 infection. The result is expected to be used for the gene therapy on AIDS, which deserves further study.