The human immune system has developed a number of innate mechanisms that can interrupt HIV infection at various stages: (i) inhibition of HIV-1 by downmodulation or blocking of the CCR5 co-receptor induced by an increase in the CC chemokines CCL3, CCL4, and CCL5 and (ii) inhibition of HIV-1 which may have escaped the CCR5-mediated mechanism by upregulation of intracellular host-encoded HIV-1 restriction factors by interfering with viral RNA reverse transcription and post-integration restriction and adherence. Here, CCR5 is linked to HIV infectious disease.