Association of KIR2DS1 and KIR2DS3 with fatal outcome in Ebola virus infection

Abstract

Zaïre ebolavirus (ZEBOV) infection rapidly outruns the host's immunity and leads to death within a week. Fatal cases have been associated with an aberrant innate, proinflammatory immune response followed by a suppressed adaptive response leading to the rapid depletion of peripheral NK cells and lymphocytes. A critical role for NK cells has been suggested but not elucidated. In this genetic study, we investigated the association of KIR genotype with disease outcome by comparing genotypes of a Gabonese control population, IgG+ contacts, survivors, and fatalities of ZEBOV infection. We showed that the activating KIR2DS1 and KIR2DS3 genes associate with fatal outcome in Ebola virus infection. In addition, this study brings supplemental evidence in favor of the specificity of the IgG+ contact population. The outcome of fulminating Ebola virus infection could depend in part on the host's inherited KIR gene repertoire. This supports a key role for KIRs in disease susceptibility to infections.

Association of Killer Cell Immunoglobulin-Like Receptor Genes with Pandemic Influenza A (H1N1)pdm09 Infection in Critically Ill Macedonian Patients

“…While there is evident predominance of KIR activating genes in the group of patients with very severe disease, these differences do not reach statistical significance. Our results suggest that activating KIR genes might be a predisposing factor for more severe viral disease and are in agreement with earlier proposed theories [50,51]. Our next step should be HLA genotyping of the samples in order to explore the ligands for the KIRs in the critically ill Macedonian patients with pandemic influenza A (H1N1)pdm09 infection.…”

“…This finding is in concordance with another recent study [51], where predominance of activating KIR genes (KIR2DS5 and KIR3DS1) was noted in severely ill patients with influenza (H1N1)pdm09 infection. It would be interesting to take into account the allelic polymorphism, which might allow different alleles to be expressed differentially and thus influence ligand binding and consecutive cytolysis [50]. Unfortunately, at present, we are not able to perform this analysis.…”

“…Comparable predominance of group Bx genotypes has been observed in many different populations, such as North Indians, Palestinians, South Asians, Afro-Caribbeans and also, general Macedonian population [46][47][48][49]. In a similar recent study analyzing the KIR polymorphisms in patients infected with Ebola virus [50], significantly higher frequencies of activating KIR2DS1 and KIR2DS3 genes were found in the group of fatally ill patients, when compared to the group of survivors from the infection. This finding led the authors to a conclusion that proposed overactivation of the NK cells was responsible for their rapid depletion.…”

Ebola-Associated Genes in the Human Genome: Implications for Novel Targets

“…The two activating KIR members, KIR2DS1 and KIR2DS3, are strongly associated with fatal outcome in the Zaire variant of EVD [48]. It is suggested that the activation of these two KIR members may cause overactivation of the immune response, leading to rapid depletion of NK cells and lymphocytes.…”

“…The KIR genes are members of Ig-superfamily of type I membrane proteins and are highly polymorphic, binding to HLA class I alleles which drive NK cell function [46,47]. Two members of the KIR activating family (KIR2DS1 and KIR2DS3) are shown to be associated with a fatal outcome in EVD [48]. The genetic association evidence for the involvement of KIR family members in EVD and other diverse diseases and disorders is shown in Supplemental Table S8.…”