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.

Highlights

  • The global human immunodeficiency virus (HIV) epidemic is easing, men who have sex with men (MSM) remain at high risk of infection [1]

  • Logistic regression was used for the multivariate analyses, adjusted for age, and we evaluated the independent contributions of the three single nucleotide polymorphisms (SNPs) to the susceptibility to and disease progression of HIV-1 infection with P values, odds ratios (ORs), and 95% confidence intervals

  • We found that genetic variation of TLR7 plays an important role in HIV-1 infection

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Summary

Introduction

The global human immunodeficiency virus (HIV) epidemic is easing, men who have sex with men (MSM) remain at high risk of infection [1]. Data from China show that the proportion of reported HIV cases infected through sexual contact has increased from 33% in 2006 to 76% by 2011, of which 14% cases were attributable to MSM [2, 3]. TLR7 Polymorphisms Affect HIV-1 Infection among MSM appears to present an increasing national public health challenge. Chen found a dynamic change of monocyte subsets and their surface markers in acute and chronic HIV-1-infected MSM individuals, indicating that dynamic states of immune response occurred during the different clinical stages [6]

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