Abstract
BackgroundNatural 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.MethodsWe 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.ResultsWe 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.ConclusionThese observations are strongly suggestive that the NK cell repertoire shaped by the KIR2DL1:HLA-C2 interaction facilitate specific infection by CHIKV.
Highlights
Chikungunya virus (CHIKV) and Dengue virus (DENV) are two mosquito-borne arboviruses transmitted by the Aedes genus
It has become increasingly clear that the strength of Killer cell immunoglobulin-like receptors (KIR)-human leukocyte antigen (HLA) interactions has functional significance, and can influence the susceptibility to or the outcome of various infectious diseases, as previously shown for human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) [12,13], yet no such associations have been uncovered in the context of CHIKV and DENV infections
We studied variations in KIR polymporphic CMH class I genotypes and associations in CHIKV, DENV2-infected patients and healthy individuals from Gabon
Summary
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 (Ogooue-Lolo and Haut-Ogooue). 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
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