Effects of TLR7 Polymorphisms on the Susceptibility and Progression of HIV-1 Infection in Chinese MSM Population

Abstract

Toll-like receptor (TLR) 7 plays a key role in innate and adaptive immunity for HIV-1 infection. We evaluated the effect of TLR7 polymorphisms on disease susceptibility and progression of HIV-1 infection in Chinese MSM (men who have sex with men). Blood samples were taken from 270 patients with laboratory confirmed HIV infection, 196 male controls were tested, and three TLR7 intronic polymorphisms (rs179010-C > T, X:12884766; rs2074109-T > C, X:12885330; and rs179009-A > G, X:12885361) were analyzed by PCR-based sequencing. The frequency of TLR7 rs179010 T allele was significantly lower in MSM patients than in controls (P = 0.039). The haplotype TTA was associated with a decreased susceptibility to HIV-1 infection (P = 0.013), especially to acute HIV-1 infection (AHI) (P = 0.002), but not to chronic HIV-1 infection (CHI). Furthermore, the haplotype TTA is linked to slow disease progression in AHI patients (P = 0.002) and a lower viral load (P = 0.042). In contrast, TLR7 rs179009 allele A contributed to a higher set point in AHI patients with rapid progression, and the frequency of rs179009 minor allele G was over-presented in CHI patients. This finding supports a role for genetic variations of TLR7 in susceptibility and disease progression of an HIV-1 infection in Chinese Han population and warrants further studies on the effect of TLR7 polymorphisms on HIV-1 infection in different populations.

Association of X-linked TLR-7 gene polymorphism with the risk of knee osteoarthritis: a case–control study

“…TLR7 gene is located on the X-chromosome 13 , which carries multiple polymorphisms potentially associated with human disease, including susceptibility and progression of HIV-1 infection, asthma, autoimmune thyroiditis, systemic lupus erythematosus (SLE) 14 – 17 . The rs3853839 C/G single-nucleotide polymorphism (SNP), which is located in the 3′ untranslated region of the TLR7, has been associated with an increase in TLR7 mRNA and protein expression, as well as upregulation of idiopathic subglottic stenosis (iSGS) 18 – 20 .…”

Single Nucleotide Polymorphisms in Genes Encoding Toll-Like Receptors 7 and 8 and Their Association with Proviral Load of SRLVs in Goats of Polish Carpathian Breed

“…Genetic studies in humans have pointed to a role for TLR SNPs, especially TLR7, in HIV infection and their association with viral loads. The presence of the most frequent TLR7 polymorphisms, TLR7 Gln11Leu (rs179008), was associated with increased viral load and altered CD4 T cell counts during HIV infection [53,54] while polymorphisms in TLR7 (re179010) and TLR8 (rs3764880) may reduce the risk of disease by participating in inhibition of viral load leading to the slower progression of infection [28,55,56]. Our results revealed that 9 out 14 identified polymorphisms were significantly associated with the SRLVs proviral concentration.…”

“…It has been found that genetic variants of TLRs can be associated with different outcome of several diseases [15,25]. Polymorphisms within TLR7 and TLR8 have been linked to susceptibility and progression of different viral diseases including these caused by Human Immunodeficiency virus (HIV-1), Hepatitis C virus (HCV), Chikungunya virus (CHIKV) and Crimean-Congo hemorrhagic fever (CCHF) virus [26][27][28][29]. Mikula et al [30,31] suggested that mutations in TLR7, TLR8 and TLR9 may play an important role as host factor predisposing sheep for infection with SRLVs.…”

Association of TLR3 gene 1377C/T (rs3775290) and TLR7 gene C/G (rs3853839) polymorphism with hand, foot, and mouth disease caused by human enterovirus 71 infection susceptibility and severity in the Chinese Han population: A meta-analysis of case-control studies

“…[ 33 – 35 ] The susceptibility, severity, and prognosis of bacterial meningitis in children and nonsmall cell lung cancer have also been proven to be related to this factor. [ 36 , 37 ] Case-control studies and meta-analyses considering TLR7 also confirmed that its polymorphism is related to the characteristics of a large number of diseases, especially immune-related diseases such as HIV-1 [ 38 ] and HBV [ 39 ] infection, tuberculosis, [ 17 ] asthma, [ 40 ] systemic lupus erythematosus, [ 41 ] and many types of cancer. [ 42 , 43 ] The main possible mechanisms were also associated with changes in dsRNA-binding capacity and inflammatory factor production related to signaling pathways, mainly NF-κB and MAPK.…”