Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.
PLoS One. 2013 Jun 14;8(6):e66253. doi: 10.1371/journal.pone.0066253. Print 2013.
Interferon regulatory factor 1 (IRF1) is induced by HIV early in the infection process and serves two functions: transactivation of the HIV-1 genome and thus replication, and eliciting antiviral innate immune responses. We previously described three IRF1 polymorphisms that correlate with reduced IRF1 expression and reduced HIV susceptibility.
To determine whether IRF1 polymorphisms previously associated with reduced HIV susceptibility play a role in HIV pathogenesis and disease progression in HIV-infected ART-naïve individuals.
IRF1 genotyping for polymorphisms (619, MS and 6516) was performed by PCR in 847 HIV positive participants from a sex worker cohort in Nairobi, Kenya. Rates of CD4+ T cell decline and viral loads (VL) were analyzed using linear mixed models.
Three polymorphisms in the IRF1, located at 619, microsatellite region and 6516 of the gene, previously associated with decreased susceptibility to HIV infection show no effect on disease progression, either measured by HIV-1 RNA levels or the slopes of CD4 decline before treatment initiation.
Whereas these three polymorphisms in the IRF1 gene protect against HIV-1 acquisition, they appear to exert no discernable effects once infection is established.
干扰素调节因子 1（IRF1）在感染过程的早期被 HIV 诱导，具有两种功能：HIV-1 基因组的转激活和复制，以及引发抗病毒的先天免疫反应。我们之前描述了三种与 IRF1 表达降低和 HIV 易感性降低相关的 IRF1 多态性。
确定先前与降低的 HIV 易感性相关的 IRF1 多态性是否在 HIV 感染的未经 ART 治疗的个体中 HIV 发病机制和疾病进展中起作用。
通过聚合酶链反应（PCR）对来自肯尼亚内罗毕性工作者队列的 847 名 HIV 阳性参与者的 IRF1 基因多态性（619、MS 和 6516）进行基因分型。使用线性混合模型分析 CD4+T 细胞下降率和病毒载量（VL）。
IRF1 基因中的三个多态性，位于基因的 619、微卫星区和 6516，先前与降低 HIV 感染易感性相关，在治疗开始前测量 HIV-1 RNA 水平或 CD4 下降斜率时，对疾病进展没有影响。
虽然这些 IRF1 基因中的三个多态性可以预防 HIV-1 获得，但一旦感染建立，它们似乎没有明显的作用。
