title: The effects of killer cell immunoglobulin-like receptor (KIR) genes on susceptibility to HIV-1 infection in the Polish population.
abstract: Killer cell immunoglobulin-like receptors (KIR) are the most polymorphic receptors of natural killer (NK) cells. Their activity diversifies the functions of NK cells in the antiviral immune response, so the presence of certain KIR may affect transmission of HIV-1. The aim of the study was to evaluate the influence of KIR genes on the susceptibility to HIV-1 infection in the Polish population depending on the route of exposure. We determined the frequencies of activating (2DS1, 2DS2, 2DS3, 2DS4f, 2DS4del, 2DS5, 3DS1) and inhibitory (2DL1, 2DL2, 2DL3, 2DL5, 3DL1) KIRs in HIV-1-positive patients (n = 459), individuals exposed to HIV-1 but uninfected (EU, n = 118) and in uninfected, healthy blood donors (BD, n = 98). Analysis was performed using stepwise logistic regression. Apart from KIRs, CCR5-∆32, and CCR2-64I, alleles were also analyzed, as we knew or suspected that these features could affect susceptibility to HIV infection. The regression confirmed the protective effect of CCR5-∆32 (OR = 0.25, p = 0.006) and CCR2-64I (OR = 0.59, p = 0.032) against HIV infection. Among KIR genes, 2DL3 was found to be a protective factor (OR = 0.30, p = 0.015). A similar effect was seen for 3DS1 but only in intravenous drug users (IDUs) (OR = 0.30, p = 0.019), not in sexually exposed people. 2DL5 was found to be a factor facilitating HIV infection (OR = 2.13, p = 0.013). A similar effect was observed for 2DL2 but only in females (OR = 2.15, p = 0.040), and 2DS1 in IDUs (OR = 3.03, p = 0.022). Our results suggest a beneficial role of KIR3DS1 and 2DL3 supporting resistance to HIV infection and a harmful effect of 2DS1, 2DL5, and 2DL2 genes promoting HIV acquisition.
authors.affiliation: Laboratory of Virology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114, Wroclaw, Poland. kjzwolinska@iitd.pan.wroc.pl.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Zwolińska
authors.affiliation: Laboratory of Virology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114, Wroclaw, Poland.
authors.forename: Olga
authors.initials: O
authors.lastname: Błachowicz
authors.affiliation: Laboratory of Virology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114, Wroclaw, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Tomczyk
authors.affiliation: Department of Infectious Diseases, Liver Diseases and Acquired Immune Deficiencies, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Brygida
authors.initials: B
authors.lastname: Knysz
authors.affiliation: Department of Infectious Diseases, Liver Diseases and Acquired Immune Deficiencies, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Gąsiorowski
authors.affiliation: Department of Infectious Diseases, Liver Diseases and Acquired Immune Deficiencies, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Zalewska
authors.affiliation: Laboratory of Virology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114, Wroclaw, Poland.
authors.forename: Beata U
authors.initials: BU
authors.lastname: Orzechowska
authors.affiliation: Laboratory of Virology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114, Wroclaw, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Sochocka
authors.affiliation: Laboratory of Virology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114, Wroclaw, Poland.
authors.forename: Egbert
authors.initials: E
authors.lastname: Piasecki
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D004198:Disease Susceptibility; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D015658:HIV Infections / Q000453:epidemiology / Q000235:genetics* / Q000821:virology; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism; D008297:Male; D011044:Poland / Q000453:epidemiology; D011110:Polymorphism, Genetic / Q000235:genetics*; D054340:Receptors, KIR / Q000235:genetics*; D054341:Receptors, KIR3DL1 / Q000235:genetics; D054347:Receptors, KIR3DL2 / Q000235:genetics; D054349:Receptors, KIR3DS1 / Q000235:genetics
chemical_list: D054340:Receptors, KIR; D054341:Receptors, KIR3DL1; D054347:Receptors, KIR3DL2; D054349:Receptors, KIR3DS1
keywords: Chemokine receptors; Host genetics; Killer cell immunoglobulin-like receptors (KIR); Susceptibility to HIV infection