title: Association of HLA class-I and inhibitory KIR genotypes in Gabonese patients infected by Chikungunya or Dengue type-2 viruses.
abstract: BACKGROUND
  Natural killer (NK) cells provide defense in the early stages of the immune response against viral infections. Killer cell immunoglobulin-like receptors (KIR) expressed on the surface of NK cells play an important role in regulating NK cell response through recognition of human leukocyte antigen (HLA) class I molecules on target cells. Previous studies have shown that specific KIR/ligand combinations are associated with the outcome of several viral infectious diseases.
  
  
  METHODS
  We investigated the impact of inhibitory and activating KIR and their HLA-class I ligand genotype on the susceptibility to Chikungunya virus (CHIKV) and Dengue virus (DENV2) infections. From April to July 2010 in Gabon, a large outbreak of CHIKV and DENV2 concomitantly occurred in two provinces of Gabon (Ogooué-Lolo and Haut-Ogooué). We performed the genotypic analysis of KIR in the combination with their cognate HLA-class I ligands in 73 CHIKV and 55 DENV2 adult cases, compared with 54 healthy individuals.
  
  
  RESULTS
  We found in CHIV-infected patients that KIR2DL1 and KIR2DS5 are significantly increased and decreased respectively, as compared to DENV2+ patients and healthy donors. The combination of KIR2DL1 and its cognate HLA-C2 ligand was significantly associated with the susceptibility to CHIKV infection. In contrast, no other inhibitory KIR-HLA pairs showed an association with the two mosquito-borne arboviruses.
  
  
  CONCLUSIONS
  These observations are strongly suggestive that the NK cell repertoire shaped by the KIR2DL1:HLA-C2 interaction facilitate specific infection by CHIKV.
authors.affiliation: Sorbonne Universités, UPMC, Univ Paris 06, CR7, CIMI-Paris, Paris, France; INSERM, U1135, CIMI-Paris, Paris, France; Centre International de Recherches Médicales de Franceville, Unité des maladies Emergentes, Franceville, Gabon.
authors.forename: Caroline
authors.initials: C
authors.lastname: Petitdemange
authors.affiliation: Sorbonne Universités, UPMC, Univ Paris 06, CR7, CIMI-Paris, Paris, France; Metabiota Inc., San Francisco, California, United States of America.
authors.forename: Nadia
authors.initials: N
authors.lastname: Wauquier
authors.affiliation: AP-HP Hôpital Pitié-Salpêtrière, Département d'Immunologie, Paris, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Jacquet
authors.affiliation: Sorbonne Universités, UPMC, Univ Paris 06, CR7, CIMI-Paris, Paris, France; INSERM, U1135, CIMI-Paris, Paris, France; AP-HP Hôpital Pitié-Salpêtrière, Département d'Immunologie, Paris, France.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Theodorou
authors.affiliation: Centre International de Recherches Médicales de Franceville, Unité des maladies Emergentes, Franceville, Gabon; IRD, Maladies Infectieuses et Vecteurs: Ecologie, Génétique, Evolution et Contrôle, Montpellier, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Leroy
authors.affiliation: Sorbonne Universités, UPMC, Univ Paris 06, CR7, CIMI-Paris, Paris, France; INSERM, U1135, CIMI-Paris, Paris, France; CNRS, ERL8255, CIMI-Paris, Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Vieillard
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D065632:Chikungunya Fever / Q000276:immunology* / Q000821:virology; D002646:Chikungunya virus / Q000276:immunology*; D003715:Dengue / Q000235:genetics / Q000276:immunology* / Q000821:virology; D003716:Dengue Virus / Q000276:immunology*; D005260:Female; D005681:Gabon; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008024:Ligands; D008297:Male; D054340:Receptors, KIR / Q000235:genetics*
chemical_list: D015395:Histocompatibility Antigens Class I; D008024:Ligands; D054340:Receptors, KIR