Association of toll-like receptor polymorphisms with acquisition of HIV infection and clinical findings

Abstract

Background: To find the relationship between toll-like receptor (TLR) gene variants and human immunodeficiency virus (HIV) infection and clinical findings, which could inform clinical decisions and vaccination strategies. Method: Four databases were searched for articles that were published on or before Jul.1, 2020. Review Manager 5.3 software was applied to perform meta-analysis to explore. Results: A total of 10 studies involving 20 genes, 3697 cases, and 6498 controls were included in this systematic review. TLR2 –196 to –174 Ins/Del (odds ratio [OR] = 1.562; P = .002), TLR4 rs4986790 (OR = 2.05; P = .002), TLR3 rs3775291 (OR = 0.25; P = .03), TLR7 rs179008 ( P = .002), TLR7 rs2074109 (OR = 0.27, P = .019) were found associated with HIV infection. TLR2 –196 to –174, TLR4 rs4986790, TLR7 rs179008, TLR8 rs3764880, TLR9 rs352140 were found associated with clinical findings of HIV infection. We identified 5 case-control studies in meta-analysis, involving 695 cases and 729 controls on TLR7 rs179008 polymorphism, totaling 652 cases and 614 controls on TLR9 rs352140 polymorphism. In meta-analysis, we employed various genetic models. The T allele of TLR7 rs179008 was conferred the risk of HIV infection (T vs A: OR = 1.25, P A = .02). An increased risk of HIV infection was found for individuals with the TLR9 rs352140 GG genotype (GG vs AA: OR = 1.50, P A = .04). Conclusions: The systematic review indicated that TLR7 rs179008 T allele provides risk effects for HIV infection. TLR9 rs352140 GG genotype may associate with HIV infection.

Role of TLRs in HIV-1 Infection and Potential of TLR Agonists in HIV-1 Vaccine Development and Treatment Strategies

“…However, interpretations of how TLR SNPs affect the immune response are further complicated by other factors including ethnicity, gender, and the possibility of multigenic effects. The molecular mechanisms by which SNPs influence TLR receptor functioning are unclear for many TLRs [ 54 ]. Recent research on TLR polymorphisms and their correlation with various outcomes, published over the last five years, is presented in this review ( Table S1 ).…”

“…However, some studies emphasise that a role of TLR2 in HIV-1 disease progression rates (CD4+ 200 cells/μL) may be distinct from this gene’s impact on infection susceptibility [ 58 ]. In 2020, Shi et al conducted a systematic review and meta-analysis of 10 studies covering 20 genes and showed a correlation between clinical findings in HIV-infected persons and TLR2 −196 to −174 Ins/Del [ 54 ]. In 2022, TLR2 , TLR4 , and TLR9 genetic diversity in HIV-1-infected patients with and without tuberculosis coinfection was studied by Kaushik et al However, no significant differences in the frequency of the C2180T allele between the healthy and patient subcategories were found.…”

“…The TLR4 rs4986791 G allele was also discovered to be a significant risk factor for HIV infection among Caucasians and four other populations examined in this meta-analysis [ 63 ]. In a systematic review and meta-analysis by Shi et al in 2020 and Kim and Jeong in 2020, found that TLR4 rs4986790 was associated with HIV infection [ 54 , 64 ]. TLR gene variants have been linked to increased or decreased susceptibility to a variety of infectious illnesses in several studies.…”

“…As recently noted by Vallejo et al, the association between the TLR9 1635AA genotype is associated with increased probability of HIV-1 rebound after ART interruption [ 77 ]. TLR9 polymorphisms are associated with the clinical presentation of HIV disease and the GG genotype has been linked to an increased risk of HIV infection [ 54 , 78 , 79 ]. A study by Shaikh et al found that the TLR9 rs352140 variant is not associated with HIV disease progression [ 71 ].…”

The TLR9 2848C/T Polymorphism Is Associated with the CMV DNAemia among HIV/CMV Co-Infected Patients

“…The findings suggest a potentially important role of host TLR9 polymorphisms in HIV disease progression [ 8 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. The TLR9 rs352140 GG genotype was associated with an increased risk of HIV infection, disease progression, and CD4 count [ 20 , 27 , 29 ]. Mutation present in at least one allele of the TLR9 1635A/G SNP (rs352140) was found to be associated with increased CMV acquisition in HIV-exposed infants [ 19 ].…”