Abstract
Toll-like receptors (TLRs) play an important role in the innate immune response to HIV infection. Single nucleotide polymorphism (SNP) in TLR7 (Gln11Leu) gene has been associated with a rapid decline of CD4T cell count. Hence, we assessed the TLR7 (rs179008, Gln11Leu (A/T) and rs179009, IVS2-151 (A/G)) polymorphism in 150 HIV-infected individuals naïve to ART and 158 healthy controls. The genotyping of TLR7 Gln11Leu (A/T) and IVS2-151 (A/G) polymorphisms was done using the PCR-RFLP method. In univariate analysis, none of the genotype and haplotype of TLR7 Gln11Leu (A/T) and IVS2-151 (A/G) polymorphism differed significantly between HIV-infected individuals and healthy controls. The occurrence of TLR7 rs179009AG genotype in the codominant model and rs179009 AG-GG genotype in the dominant model was significantly reduced in HIV-infected individuals as compared to healthy controls (18.0% vs. 29.1%, OR = 0.42, P = 0.016; 26.7% vs. 36.7%, OR = 0.52, P = 0.016). TLR7 rs179009AG genotype was significantly underrepresented in the intermediate HIV disease stage compared with healthy controls (OR = 0.03, P = 0.04). TLR7 rs179009AG genotype expressed higher in tobacco-consuming HIV-infected individuals compared with nonusers (OR = 1.71, P = 0.47). In conclusion, rs179009 AG-GG and AG genotypes were found reduced in HIV-infected individuals as compared to healthy controls; their higher prevalence in health individuals clearly support that they are associated with reduced risk of acquisition of HIV-1 infection.
Highlights
In India, HIV remains to be one of the major issues (WHO, HIV/AIDS Fact sheet November 2017)
AG-GG genotype in the dominant model, and rs179009 AG genotype in the overdominant model was significantly reduced in HIV-infected individuals as compared to healthy controls (18.0% vs. 29.1%, Odds ratios (ORs) = 0:42, 95% confidence interval (CI): 0.23-0.77, P = 0:016; 26.7% vs. 36.7%, OR = 0:52, 95% CI: 0.30-0.89, P = 0:016, and 18% vs. 29.1%, OR = 0:42, 95% CI: 0.230.77, P = 0:0039)
From India, this is a first of its kind study that examined the likely effects of TLR7 polymorphisms on susceptibility to the acquisition of HIV-1 and disease progression
Summary
In India, HIV remains to be one of the major issues (WHO, HIV/AIDS Fact sheet November 2017). The difference in susceptibility to the acquisition of HIV and disease progression is associated with a genetic background [1]. Innate immunity is known to play a crucial role in response to viral pathogens [2]. Toll-like receptors (TLRs) are pathogen recognition receptors (PRRs) that play a pivotal role in the innate immune system and control inflammatory responses and adaptive immunity [3]. PRRs recognize evolutionarily conserved pathogen-associated molecular patterns (PAMPs), and PAMP recognition triggers activation of signal transduction pathways and downstream effector responses [4, 5]. TLR families like TLR1, TLR2, TLR4, and TLR6 are localized on the cell surface and TLR3, TLR7, TLR8, and TLR9 are localized in endosomal membranes inside the cell [4, 5]
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