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      KIR2DL2, KIR2DL5A and KIR2DL5B Genes Induce Susceptibility to Dengue Virus Infection, while KIR3DL3 and KIR2DS5 Confer Protection

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          Abstract

          Background and Objectives

          Dengue fever (DF), an emerging and re-emerging viral disease, is a major public health problem. The aim of this study was to investigate the influence of KIRs genes polymorphism and KIRs genotypes in susceptibility to dengue virus infection and disease severity in a population from Burkina Faso through a case-control study.

          Methods

          KIRs genes determination was performed using PCR-SSP in 50 patients infected by dengue virus (DENV) and 54 Healthy controls (HC) subjects who had never been infected.

          Results

          Data analysis showed significant association between frequencies of three KIR genes and dengue virus infection (DF): KIR2DL2 (OR: 7.32; IC: 2.87–18.65; P < 0.001); KIR2DL5A (OR: 15.00, IC: 5.68–39.59; P < 0.001) and KIR2DL5B (OR: 11.43; IC: 4.42–29; P < 0.001). While, KIR3DL3 (OR: 0.13, IC: 0.052–0.32; P < 0.001) and KIR2DS5 (OR: 0.12; IC: 0.04–0.30; P < 0.001) were associated with protection against DF. KIR2DL4 (OR: 9.75; IC95%: 1.33–70.97; p: 0.03) and KIRD3DL1 (OR: 12.00; IC95%: 1.60–90.13; p: 0.02) were associated with an increased risk in the development of secondary dengue infection (SDI).

          Conclusion

          The results suggest a contribution of KIR2DL2, KIR2DL5A, and KIR2DL5B genes in the susceptibility of DF development. In contrast, KIR3DL3 and KIR2DS5 were associated with protection against DF development by enhancing both innate and acquired immune responses.

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          Most cited references33

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          The Yin and Yang of HLA and KIR in human disease.

          Killer cell immunoglobulin-like receptors (KIR) are expressed on natural killer (NK) cells and subsets of T cells. The KIR genes are polymorphic and the KIR gene complex is polygenic with varying numbers of inhibitory and activating receptors. HLA class I molecules serve as ligands for the KIR. Interactions of the independently segregating KIR and HLA loci are important for recognition of targets by NK cells as well as NK cell 'licensing'. Several disease association studies indicate a role for interactions between these loci in infectious diseases, autoimmune/inflammatory disorders, cancer and reproduction. Emerging functional data supports a mechanism based on a continuum of inhibition to activation through various compound KIR-HLA genotypes in diseases.
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            Dengue in the early febrile phase: viremia and antibody responses.

            A multicenter effort was begun in 1994 to characterize the pathophysiology of dengue using a study design that minimized patient selection bias by offering enrollment to all children with undifferentiated fever for <72 h. In the first year, 189 children were enrolled (age range, 8 months to 14 years). Thirty-two percent of these children had dengue infections (60 volunteers). The percentage of children with a secondary dengue infection was 93%, with only 4 (7%) having a primary dengue infection. The virus isolation rate from the plasma of children with dengue was 98%. Viremia correlated highly with temperature. All four dengue virus serotypes were isolated at both study sites. This study demonstrates that all four serotypes of dengue virus can cause dengue hemorrhagic fever, that all dengue patients as defined by serology experience viremia during the febrile phase, and that as fever subsides, so does viremia.
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              The killer immunoglobulin-like receptor gene cluster: tuning the genome for defense.

              Killer immunoglobulin-like receptors (KIRs) are molecules expressed on the surface of natural killer (NK) cells, which play an important role in innate immunity. KIR recognition of major histocompatability complex (MHC) class I allotypes represents one component of the complex interactions between NK cells and their targets in determining NK cell reactivity. KIRs are encoded by a gene cluster at human chromosome 19q13.4. Despite their high degree of sequence identity, KIR genes encode proteins that have diverse recognition patterns (specific HLA class I allotypes) and confer opposing signals (activating or inhibitory) to the NK cell. The KIR gene cluster is highly polymorphic, with individual genes exhibiting allelic variability and individual haplotypes differing in gene content. The polymorphism of the KIR locus parallels that of the MHC, facilitating the adaptation of the immune system to a dynamic, challenging environment. This variation is associated with a growing number of human diseases, which is likely to extend to levels observed for the HLA loci. Here we review current progress in understanding KIR biology and genetics.
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                Author and article information

                Journal
                Mediterr J Hematol Infect Dis
                Mediterr J Hematol Infect Dis
                Mediterranean Journal of Hematology and Infectious Diseases
                Mediterranean Journal of Hematology and Infectious Diseases
                Università Cattolica del Sacro Cuore
                2035-3006
                2022
                01 November 2022
                : 14
                : 1
                : e2022075
                Affiliations
                [1 ]Universite Joseph KI-ZERBO, Laboratoire de Biologie Moleculaire et de Genetique (LABIOGENE), P.O. Box 7021, Ouagadougou 03, Burkina Faso
                [2 ]Centre de Recherche Biomoleculaire Pietro Annigoni (CERBA), P.O. Box 364, Ouagadougou 01, Burkina Faso
                [3 ]Universite Saint Thomas d’Aquin, Saaba 06 BP 10212 Ouagadougou 06
                [4 ]Centre National de la Recherche Scientifique et Technologique (CNRST), 03 BP. 7047, Ouagadougou, Burkina Faso
                [5 ]Department of Microbiology and Immunology, School of Medical Sciences, University of Cape Coast, PMB, Cape Coast, Ghana
                Author notes
                Correspondence to: Dr. Florencia Wendkuuni Djigma. Universite Joseph KI-ZERBO, Laboratoire de Biologie Moleculaire et de Genetique (LABIOGENE), P.O. Box 7021, Ouagadougou 03, Burkina Faso, Burkina Faso. Tel; 00226 70 58 56 33; E-mail: florencia.djigma@ 123456gmail.com
                Article
                mjhid-14-1-e2022075
                10.4084/MJHID.2022.075
                9652005
                36425145
                675647fe-d16e-4558-9cb8-a3585ae23f4a
                Copyright @ 2022

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by-nc/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 04 July 2022
                : 13 October 2022
                Categories
                Original Article

                Infectious disease & Microbiology
                dengue infection,kirs genes,haplotype,ssp-pcr,burkina faso
                Infectious disease & Microbiology
                dengue infection, kirs genes, haplotype, ssp-pcr, burkina faso

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