Toll样受体7（Gln11Leu）和Toll样受体9（1635A/G）单核苷酸多态性与HIV感染期间较高的CD4 T细胞计数的关联。
Association of single-nucleotide polymorphisms in TLR7 (Gln11Leu) and TLR9 (1635A/G) with a higher CD4T cell count during HIV infection.
作者信息
Said E A, Al-Yafei F, Zadjali F, Hasson S S, Al-Balushi M S, Al-Mahruqi S, Koh C Y, Al-Naamani K, Al-Busaidi J Z, Idris M A, Balkhair A, Al-Jabri A A
机构信息
Department of Microbiology and Immunology, College of Medicine and Health Sciences, Sultan Qaboos University, P.O. Box: 35, Code: 123, Muscat, Oman.
Department of Microbiology and Immunology, College of Medicine and Health Sciences, Sultan Qaboos University, P.O. Box: 35, Code: 123, Muscat, Oman.
出版信息
Immunol Lett. 2014 Jul;160(1):58-64. doi: 10.1016/j.imlet.2014.04.005. Epub 2014 Apr 16.
BACKGROUND
Toll-like receptors (TLRs) are essential elements of the innate immune response to different infections including HIV-1 infection. The single-nucleotide polymorphisms (SNPs) in TLRs have been associated with CD4T cell count and HIV disease progression. The TLR7 (Gln11Leu) SNP was shown to be associated with a rapid decline of CD4T cell count. A relation between TLR9 (1635A/G) SNP and CD4T cells count in HIV-infected patients is suggested, although the outcome associated with this SNP is still controversial.
OBJECTIVES
To determine the relation of the TLR7 (Gln11Leu) and TLR9 (1635A/G) SNPs with the damage to the immune system during HIV infection as reflected by the average CD4T cell count.
METHODS
A total of 63 HIV-infected patients and 100 healthy individuals (controls) were enrolled in this study. The above named SNPs were analyzed after amplification of the regions that potentially contain the SNPs by polymerase chain reaction (PCR) and sequencing of the PCR products. The frequency of these SNPs and their relation with the CD4T cell count were investigated.
RESULTS
The TLR7 (AA) genotype 'Gln' had a trend toward being associated with a CD4T cell count >400cells/μl after controlling viremia via HAART. Additionally, the TLR9 1635 (GG) genotype was associated with a low average CD4T cell count and the TLR9 1635 (AG) genotype was significantly related to a higher average CD4T cell count during the viremic period in HIV-infected patients.
CONCLUSION
The results of this longitudinal study supports the presence of an association between the TLR9 (1635A/G) genotype and the CD4T cell count, which helps clarifying the controversial results regarding this association. It also suggests that the CD4T cell count during the viremic period might be linked to the combination of both TLR7 (Gln11Leu) and TLR9 (1635A/G) genotypes. These results may help predicting the damage to the immune system, and thus impacting the planning for novel anti-HIV strategies.
背景
Toll样受体（TLRs）是对包括HIV-1感染在内的不同感染产生固有免疫反应的关键要素。TLRs中的单核苷酸多态性（SNPs）与CD4T细胞计数及HIV疾病进展相关。TLR7（Gln11Leu）SNP被证明与CD4T细胞计数的快速下降有关。尽管与该SNP相关的结果仍存在争议，但有研究表明TLR9（1635A/G）SNP与HIV感染患者的CD4T细胞计数之间存在关联。
目的
通过平均CD4T细胞计数来确定TLR7（Gln11Leu）和TLR9（1635A/G）SNPs与HIV感染期间免疫系统损伤的关系。
方法
本研究共纳入63例HIV感染患者和100名健康个体（对照组）。通过聚合酶链反应（PCR）扩增可能包含SNPs的区域并对PCR产物进行测序，分析上述SNPs。研究这些SNPs的频率及其与CD4T细胞计数的关系。
结果
在通过高效抗逆转录病毒治疗（HAART）控制病毒血症后，TLR7（AA）基因型“Gln”有与CD4T细胞计数>400个/μl相关的趋势。此外，在HIV感染患者的病毒血症期，TLR9 1635（GG）基因型与较低的平均CD4T细胞计数相关，而TLR9 1635（AG）基因型与较高的平均CD4T细胞计数显著相关。
结论
这项纵向研究的结果支持TLR9（1635A/G）基因型与CD4T细胞计数之间存在关联，这有助于澄清关于这种关联的有争议的结果。研究还表明，病毒血症期的CD4T细胞计数可能与TLR7（Gln11Leu）和TLR9（1635A/G）基因型的组合有关。这些结果可能有助于预测免疫系统的损伤，从而影响新型抗HIV策略的规划。
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