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.

KIR2DL2/C1 is a Risk Factor for Chronic Infection and Associated with Non-response to PEG-IFN and RBV Combination Therapy in Hepatitis C Virus Genotype 1b Patients in China

“…In the early stages of virus infection and development, the elimination of viruses in the body also depends on innate immunity, including NK cells. The killing ability of NK cells carrying KIR2DL2 may be impaired, which has also been verified in studies on KIR2DL2 and HIV (Zwolinska et al 2016). In this study, one possibility is that the inhibition of virus infection mediated by KIR2DL2 can overcome the activation of NK cells by IFN-alpha and decrease the antiviral ability of NK cells.…”

Association between killer cell immunoglobulin‐like receptor 2DS5 gene with essential hypertension in the Chinese Han patients

“…In this study, KIR2DS5 has been showed as a protective factor for essential hypertension in researched population. As far as we know, KIR2DS5 exhibits an immune activating function either in cytomegalovirus (Alvarado‐Hernandez et al., ) or human immunodeficiency virus‐1 (Zwolinska et al., ) infection, yet in essential hypertension patients, KIR2DS5 plays a protective role. We double checked all data and repeated all experiments; the results of this study still show that some unknown mechanism we did not know about essential hypertension or natural killer cells activating might be hidden and wait for deeply study to discover.…”

Spectrum and Frequency of Nk Cell Receptor Genes Among Cystic Fibrosis Patients

“…As CF is accompanied by severe infectious lesions of the upper respiratory tract, the treatment of which is far from always effective, it cannot be ruled out, that the genetically induced weakness of the activating receptor site of natural killer cells is affecting this process. It should be noted, that we did not meet such studies in the literature, but based on literary data, which relate mainly to HIV infection [23][24][25] and hepatitis C [26][27][28][29][30], it can be concluded, that the more gentle progression of the disease correlates with increased activation of the functional activity of NK cells.…”