Innate partnership of HLA-B and KIR3DL1 subtypes against HIV-1

Allotypes of the natural killer (NK) cell receptor KIR3DL1 vary in both NK cell expression patterns and inhibitory capacity upon binding to their ligands, HLA-B Bw4 molecules, present on target cells. Using a sample size of over 1,500 human immunodeficiency virus (HIV)+ individuals, we show that various distinct allelic combinations of the KIR3DL1 and HLA-B loci significantly and strongly influence both AIDS progression and plasma HIV RNA abundance in a consistent manner. These genetic data correlate very well with previously defined functional differences that distinguish KIR3DL1 allotypes. The various epistatic effects observed here for common, distinct KIR3DL1 and HLA-B Bw4 combinations are unprecedented with regard to any pair of genetic loci in human disease, and indicate that NK cells may have a critical role in the natural history of HIV infection

Memory for emotional faces in major depression following judgement of physical facial characteristics at encoding

The aim of the present study was to establish if patients with major depression (MD) exhibit a memory bias for sad faces, relative to happy and neutral, when the affective element of the faces is not explicitly processed at encoding. To this end, 16 psychiatric out-patients with MD and 18 healthy, never-depressed controls (HC) were presented with a series of emotional faces and were required to identify the gender of the individuals featured in the photographs. Participants were subsequently given a recognition memory test for these faces. At encoding, patients with MD exhibited a non-significant tendency towards slower gender identification (GI) times, relative to HC, for happy faces. However, the GI times of the two groups did not differ for sad or neutral faces. At memory testing, patients with MD did not exhibit the expected memory bias for sad faces. Similarly, HC did not demonstrate enhanced memory for happy faces. Overall, patients with MD were impaired in their memory for the faces relative to the HC. The current findings are consistent with the proposal that mood-congruent memory biases are contingent upon explicit processing of the emotional element of the to-be-remembered material at encoding

HLA-C cell surface expression and control of HIV/AIDS correlate with a variant upstream of HLA-C.

A variant 35 kb upstream of the HLA-C gene (-35C/T) was previously shown to associate with HLA-C mRNA expression level and steady-state plasma HIV RNA levels. We genotyped this variant in 1,698 patients of European ancestry with HIV. Individuals with known seroconversion dates were used for disease progression analysis and those with longitudinal viral load data were used for viral load analysis. We further tested cell surface expression of HLA-C in normal donors using an HLA-C-specific antibody. We show that the -35C allele is a proxy for high HLA-C cell surface expression, and that individuals with high-expressing HLA-C alleles progress more slowly to AIDS and control viremia significantly better than individuals with low HLA-C expressing alleles. These data strongly implicate high HLA-C expression levels in more effective control of HIV-1, potentially through better antigen presentation to cytotoxic T lymphocytes or recognition and killing of infected cells by natural killer cells