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Programmed cell death-1 single-nucleotide polymorphism rs10204525 is associated with human immunodeficiency virus type 1 RNA viral load in HIV-1-infected Moroccan subjects
Medical Microbiology and Immunology ( IF 5.5 ) Pub Date : 2021-05-24 , DOI: 10.1007/s00430-021-00712-7
Hanâ Baba 1, 2 , Anass Kettani 2 , Meryem Bouqdayr 1, 2 , Ahd Ouladlahsen 3 , Rajaa Bensghir 3 , Latifa Marih 3 , Mustapha Sodqi 3 , Soumaya Benjelloun 4 , Sayeh Ezzikouri 4 , Imane Zaidane 4 , Fatima-Zahra Jadid 4 , Kamal Marhoum El Filali 3 , Lahcen Wakrim 1
Affiliation  

Human Immunodeficiency Virus (HIV-1) infections are characterized by dysfunctional cellular and humoral antiviral immune responses. The progressive loss of effector functions in chronic viral infection has been associated with the up-regulation of programmed death-1 (PD-1), a negative regulator of activated T cells and Natural Killer cells. In HIV-1 infection, increased levels of PD-1 expression correlate with CD8 + T-cell exhaustion. In vitro, PD-1 blockade using PD-1 antibodies led to an increase in HIV-1 specific CD8 + T and memory B cell proliferation. We aimed to investigate the impact of PDCD1 rs10204525 polymorphism on HIV-1 susceptibility, AIDS development, and treatment response outcomes in HIV-1 infection in a Moroccan population. A total of 214 HIV-1 seropositive and 250 seronegative subjects were enrolled to investigate the association between the between the single-nucleotide polymorphism (SNP) rs10204525 of PDCD1 gene and HIV-1 pathogenesis using a predesigned TaqMan SNP genotyping assay. No significant association was found between rs10204525 and susceptibility to HIV-1 infection and AIDS development (p > 0.05). Genotype frequencies were significantly associated with the viral load before ART (p = 0.0105). HIV-1 viral load was significantly higher among subjects with the CC compared to TT genotype (p = 0.0043). In treated subjects, the median of viral load levels was significantly higher in CC and CT groups than TT subjects (p < 0.005). However, analysis of the correlation between CD4 + T-cell levels and PDCD1 polymorphism before and after ART showed no significant difference (p > 0.05). Our results demonstrated that rs10204525 polymorphism does not affect HIV-1 infection. However, this polymorphism may affect the response to treatment as measured by RNA viral load levels.



中文翻译:

程序性细胞死亡-1 单核苷酸多态性 rs10204525 与 HIV-1 感染的摩洛哥受试者的人类免疫缺陷病毒 1 型 RNA 病毒载量有关

人类免疫缺陷病毒 (HIV-1) 感染的特征是细胞和体液抗病毒免疫反应功能失调。慢性病毒感染中效应子功能的逐渐丧失与程序性死亡 1 (PD-1) 的上调有关,PD-1 是活化 T 细胞和自然杀伤细胞的负调节因子。在 HIV-1 感染中,PD-1 表达水平的增加与 CD8 + T 细胞耗竭相关。在体外,使用 PD-1 抗体阻断 PD-1 导致 HIV-1 特异性 CD8 + T 和记忆 B 细胞增殖增加。我们旨在调查PDCD1的影响rs10204525 摩洛哥人群 HIV-1 感染的 HIV-1 易感性、AIDS 发展和治疗反应结果的多态性。总共招募了 214 名 HIV-1 血清阳性和 250 名血清阴性受试者,以 使用预先设计的 TaqMan SNP 基因分型测定研究PDCD1基因的单核苷酸多态性 (SNP) rs10204525与 HIV-1 发病机制之间的关联 。rs10204525 与 HIV-1 感染易感性和 AIDS 发展之间未发现显着关联(p  > 0.05)。基因型频率与 ART 前的病毒载量显着相关(p  = 0.0105)。与 TT 基因型相比,CC 受试者的 HIV-1 病毒载量显着更高(p = 0.0043)。在接受治疗的受试者中,CC 和 CT 组的病毒载量水平中位数显着高于 TT 受试者 ( p  < 0.005)。然而, ART前后CD4+T细胞水平与PDCD1多态性的相关性分析 显示无显着差异(p  >0.05)。我们的结果表明 rs10204525 多态性不影响 HIV-1 感染。然而,这种多态性可能会影响通过 RNA 病毒载量水平衡量的治疗反应。

更新日期:2021-05-25
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