Protective KIR-HLA interactions for HCV infection in intravenous drug users

Abstract

Intravenous drug use has become the principal route of hepatitis C virus (HCV) transmission due to the sharing of infected needles. In this study, we analyzed the distribution of HLA-KIR genotypes among 160 Puerto Rican intravenous drug users (IDUs) with HCV infection and 92 HCV-negative Puerto Rican IDUs. We found a significant association between the presence of different combinations of KIR inhibitory receptor genes (KIR2DL2 and/or KIR2DL3, pC=0.01, OR=0.07; KIR2DL2 and/or KIR2DL3+KIR2DS4, pC=0.01, OR=0.39) and HLA-C1 homozygous genotypes (HLA-C1+KIR2DS4, pC=0.02, OR=0.43; HLA-C1+KIR2DL2+KIR2DS4, pC=0.02, OR=0.40) together with the activating receptor KIR2DS4 (HLA-C1+KIR2DS4+KIR2DL3 and/or KIR2DL2, pC=0.004, OR=0.38) with protection from HCV infection. Our findings in HCV-infected and non-infected IDUs suggest an important role for KIRs (KIR2DL2 and KIR2DL3) with group HLA-C1 molecules, in the presence of activating KIR2DS4, in protection from HCV infection. These results support the hypothesis that activator signaling, mediated by KIR2DS4, plays a determinant role in the regulation of NK cell antiviral-activity.

Figure 1

Individual admixture estimates in HCV-infected IDU’s (red circles) and non-infected IDU’s (dark blue circles) of Puerto Rican ethnic background. Admixture estimates, using STR markers in a tri-hybrid model, demonstrated 73.5 % of European, 16% of African, and 10.4% of American Indian contribution in Puerto Ricans living in Massachusetts. The parental populations are represented in each cluster (corners of the triangle): Cluster 1: represents European parental population (green circles); Cluster 2: West African parental population (light blue circles) and; “All others”: The indigenous parental population (Yellow circles).