title: 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.
authors: Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City, Mexico.
authors: Joaquín
authors: J
authors: Zúñiga
authors: Viviana
authors: V
authors: Romero
authors: José
authors: J
authors: Azocar
authors: Daniel
authors: D
authors: Terreros
authors: María Inés
authors: MI
authors: Vargas-Rojas
authors: Diana
authors: D
authors: Torres-García
authors: Luis
authors: L
authors: Jiménez-Alvarez
authors: Gilberto
authors: G
authors: Vargas-Alarcón
authors: Julio
authors: J
authors: Granados-Montiel
authors: Zaheed
authors: Z
authors: Husain
authors: Raymond T
authors: RT
authors: Chung
authors: Chester A
authors: CA
authors: Alper
authors: Edmond J
authors: EJ
authors: Yunis
mesh_terms: D016000:Cluster Analysis; D005787:Gene Frequency; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D015236:HLA-C Antigens / Q000235:genetics; D006526:Hepatitis C / Q000235:genetics* / Q000821:virology; D006801:Humans; D054340:Receptors, KIR / Q000235:genetics*; D054343:Receptors, KIR2DL2 / Q000235:genetics; D054344:Receptors, KIR2DL3 / Q000235:genetics; D015819:Substance Abuse, Intravenous / Q000235:genetics* / Q000821:virology
chemical_list: D006680:HLA Antigens; D015236:HLA-C Antigens; C515077:KIR2DL2 protein, human; C515078:KIR2DL3 protein, human; C473953:KIR2DS4 protein, human; D054340:Receptors, KIR; D054343:Receptors, KIR2DL2; D054344:Receptors, KIR2DL3