New Knowledge About CCR5, HIV Infection, and Disease Progression: Is "Old" Still Valuable?

C-C chemokine receptor (CCR) 5 (CCR5) is the main HIV-1 coreceptor involved in virus entry and cell-to-cell spread during acute and chronic infections: such CCR5 and T cell tropic viruses are adapted to and replicate in CD4⁺ memory T cells. Polymorphisms in CCR5 regulate CCR5 expression, which, in turn, influences HIV infection acquisition and subsequent disease progression. Among these polymorphisms, a 32-bp deletion in the CCR5 open reading frame (CCR5 Δ32) and a single nucleotide polymorphism (SNP) in the promoter (-2459G/A) are the most well-characterized polymorphisms. CCR5 Δ32 provides partial to full protection against HIV infection and, therefore, serves as a basis for gene deletion studies attempting to achieve a permanent HIV cure. Recent studies have discovered that certain SNPs in the CCR region, not within CCR5, also affect CCR5 expression, HIV infection, and disease progression. Although these studies provide further valuable information regarding the role of human genetic variation in HIV/AIDS, they did not incorporate -2459G/A. In this article, the author summarizes the knowledge gained through the discovery of these new SNPs and introduces the idea that by not incorporating -2459G/A, less comprehensive conclusions may have been reached. Until a strategy that delivers a cure to the millions is found, every piece of information that may help curtail the HIV/AIDS threat to public health should be considered useful.