Protective KIR-HLA interactions for HCV infection in intravenous drug users.
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.
Zúñiga
Joaquín
J
Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Mexico City, Mexico.
Romero
Viviana
V
Azocar
José
J
Terreros
Daniel
D
Vargas-Rojas
María Inés
MI
Torres-García
Diana
D
Jiménez-Alvarez
Luis
L
Vargas-Alarcón
Gilberto
G
Granados-Montiel
Julio
J
Husain
Zaheed
Z
Chung
Raymond T
RT
Alper
Chester A
CA
Yunis
Edmond J
EJ
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
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