CCR5 antisense RNA (CCR5AS)

CCR5 antisense RNA (CCR5AS) is a long non-coding RNA transcribed from the antisense strand of the *CCR5* gene locus. CCR5AS regulates the expression levels of the CCR5 chemokine receptor on immune cells, particularly CD4+ T cells, by interfering with the RNA-binding protein Raly, which would otherwise promote the degradation of CCR5 mRNA. Genetic variation (notably rs1015164) upstream of the CCR5AS locus influences its expression, which in turn affects CCR5 availability on the cell surface—a key determinant of susceptibility to infection by CCR5-tropic HIV-1. High CCR5AS expression stabilizes CCR5 mRNA, increasing the number of CCR5 receptors and heightening HIV susceptibility; conversely, knockdown of CCR5AS reduces CCR5 surface expression and impairs the ability of HIV-1 to infect cells. CCR5AS represents a rare example of a lncRNA exerting clinically relevant regulatory effects on a well-known immune receptor, although it is not itself the target of approved therapies[1].

Other names

CCR5ASRP11-24F11.2 (gene name)

Not applicable directly to drugs—but knockdown/inhibition of CCR5AS leads to decreased CCR5 expression on CD4+ T cells, thus reducing susceptibility to CCR5-tropic HIV-1 infection