The emerging role of HLA-C in HIV-1 infection

Recently, genome-wide association studies have identified the major histocompatibility complex class I protein HLA-C as an important molecule that affects HIV disease progression. The association between HLA-C and HIV disease outcome was originally determined through a single nucleotide polymorphism (SNP) 35 kb upstream of the HLA-C locus. More recent work has focused on elucidating the functional significance of the -35 SNP, and several groups now have demonstrated HLA-C surface expression to be a key element in control of HIV viral load, with higher surface expression associating with slower disease progression. Most recently, control of HLA-C surface expression has been correlated with the presence of microRNA binding sites that affect HLA-C expression and control of HIV disease. This review highlights these results and explores the ways in which HLA-C surface expression could affect immune system function in the setting of HIV disease.