Strong Association of the rs4986790 Single Nucleotide Polymorphism (SNP) of the Toll-Like Receptor 4 (TLR4) Gene with Human Immunodeficiency Virus (HIV) Infection: A Meta-Analysis

Yong-Chan Kim,Byung-Hoon Jeong

doi:10.3390/genes12010036

Abstract

Human immunodeficiency virus (HIV) causes acquired immune deficiency syndrome (AIDS) and enters the host cell via CD4 and either CC-chemokine receptor 5 (CCR) or CXC-chemokine receptor 4 (CXCR4). HIV is directly recognized by toll-like receptor 4 (TLR4) and affects downstream immune-related signal pathways. In addition, stimulated TLR4 inhibits HIV-1 invasion, and the rs4986790 single nucleotide polymorphism (SNP) (D299G) of the TLR4 gene contributes to the risk of HIV-1 infection in an Indian population. To evaluate whether the rs4986790 SNP of the TLR4 gene is related to vulnerability to HIV-1 infection, we collected genetic information from HIV-1 patients in previous studies and performed an association analysis with a matched control population obtained from the 1000 Genomes Project. In addition, to strengthen the results of association analysis, we performed a meta-analysis. We identified a strong association between the rs4986791 SNP and susceptibility to HIV infection in HIV-infected patients in previous studies and a matched control population obtained from the 1000 Genomes Project. In addition, we found that the G allele of the rs4986791 SNP in the TLR4 gene is strongly related to susceptibility to HIV infection in three Caucasian populations (odd ratio = 2.29, 95% confidence interval: 1.72–3.07, p = 1.438 × 10−7) and all four populations (odd ratio = 2.22, 95% confidence interval: 1.74–2.84, p = 2 × 10−10) in a meta-analysis. To the best our knowledge, this was the first meta-analysis on the association between the rs4986791 SNP of the TLR4 gene and susceptibility to HIV infection.

Highlights

Human immunodeficiency virus (HIV) is a retrovirus that harbors positive sense single strand RNA as its viral genome
Among toll-like receptors (TLRs), a previous study reported that toll-like receptor 4 (TLR4) located on the cell surface was upregulated in response to HIV-1 infection in monocyte-derived macrophage (MDM)
To identify an association between the rs4986790 single nucleotide polymorphism (SNP) (D299G) and susceptibility to HIV infection, we performed an association analysis between HIV patients for whom information on ethnic background and allele frequencies of rs4986790 SNP of the TLR4 gene were reported in previous studies [14–16] and matched Caucasian control populations, Genes 2021, 12, x FOR PEER REVIEWincluding Iberian populations in Spain, Tuscans from Italy and northern and western

Summary

Introduction

Human immunodeficiency virus (HIV) is a retrovirus that harbors positive sense single strand RNA as its viral genome. It has been postulated that HIV originated from nonhuman primates and spread to humans through certain body fluids, including blood, semen, vaginal or rectal fluids and breast milk during the 1900s. HIV is internalized by host cells using host receptor proteins, including CD4 and either CC-chemokine receptor. HIV mainly targets CD4+ T cells and can lead acquired immune deficiency syndrome (AIDS) by disarming the host immune system [3,4]. Several pattern recognition receptors (PRRs) including toll-like receptors (TLRs), RIG-I-like receptors (RLRs) and NOD-like receptors (NLRs), recognize a pathogen-related pattern of external invaders and activate the host immune system through downstream regulators, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), mitogen-activated protein kinase (MAPK) and interferon type I [5–9]. Among TLRs, a previous study reported that TLR4 located on the cell surface was upregulated in response to HIV-1 infection in monocyte-derived macrophage (MDM)

Methods

Results

Discussion

Conclusion