Killer-cell immunoglobulin-like receptors (KIR) in severe A (H1N1) 2009 influenza infections

Abstract

Introduction of a novel influenza virus into the human population leads to the occurrence of pandemic events, such as the one caused by pandemic influenza A (H1N1) 2009 virus. The severity of infections caused by this virus in young adults was greater than that observed in patients with seasonal influenza. Fatal cases have been associated with an abnormal innate, proinflammatory immune response. A critical role for natural killer cells during the initial responses to influenza infections has been suggested. In this study, we assessed the association of killer-cell immunoglobulin-like receptors (KIRs) with disease severity by comparing KIR gene content in patients with mild and severe pandemic influenza virus infections to a control group. We found that activator (KIR3DS1 and KIR2DS5) and inhibitory (KIR2DL5) genes, encoded in group B haplotypes containing the cB01, cB03 and tB01 motifs, are associated with severe pandemic influenza A (H1N1) 2009 infections. Better understanding of how genetic variability contributes to influenza virus pathogenesis may help to the development of immune intervention strategies aiming at controlling the severity of disease.

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

“…Although for the KIR2DS1 gene, we find "inverse" situation with these gene being more frequent in the control group, we still find this hypothesis tempting and possible, since as patients when compared to the healthy subjects. 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].…”

“…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.…”

Role of KIR3DS1 in human diseases

“…While no evidence for the participation of KIR3DS1 in control of HTLV-1 infection was found (O’Connor et al, 2012), carriage of KIR3DS1 and other haplotype B containing KIRs was associated with severe pandemic influenza A (H1N1) 2009 infections (Aranda-Romo et al, 2012). Frequencies of KIR3DS1 as well as KIR2DS1 and KIR2DL5 were furthermore increased in a group of patients who spontaneously recovered from HBV compared to individuals with chronic HBV infection or healthy controls (Zhi-Ming et al, 2007).…”

Protection From Varicella Zoster in Solid Organ Transplant Recipients Carrying Killer Cell Immunoglobulin-Like Receptor B Haplotypes

“…Laurent Schmied, 1 Grzegorz Terszowski, 1 Asensio Gonzalez, 1 Karin Schmitter, 1 Hans H. Hirsch, 2,3 Christian Garzoni, 4,5 Christian van Delden, 6 Katia Boggian, 7 Nicolas J. Mueller, 8 Christoph Berger, 9 Jean Villard, 10 Oriol Manuel, 11 Pascal Meylan, 11 Christoph Hess, 12 Martin Stern, 1 …”

“…6,7 More recently, several studies have suggested that KIR genes may also associate with the risk for other viral infections, such as hepatitis C, 8 herpes simplex, 9 BK polyomavirus (BKPyV), 10 and influenza. 11 For Epstein-Barr virus (EBV) and varicella zoster virus (VZV), 2 further members of the human herpes virus family, evidence for involvement of NK cells in disease control recently emerged, but no possible correlation with KIR genotype has been investigated yet. 12,13 For several of the abovementioned viruses, different receptors were shown to be involved in the innate immune response.…”