In summary, we provide the first evidence in relevant infection models with a dual tropic HIV-1 that can efficiently infect primary human PBMC when its binding to CCR5 is blocked genetically or pharmacologically, demonstrating CCR5 interaction with dual-tropic HIV-1 Env played a significant role in Env-induced depletion of bystander CD4 T cells. This evidence concerns the gene CCR5 and infection.