Verma M K, Shakya S
Department of Biotechnology, Acharya Nagarjuna University, Nagarjuna Nagar, Guntur, Andhra Pradesh, 522510, India.
Indian Institute of Technology Indore, Indore, Madhya Pradesh, 453552, India.
Genes Dis. 2020 Apr 18;8(4):475-483. doi: 10.1016/j.gendis.2020.04.007. eCollection 2021 Jul.
Chemokines are small protein molecules associated with various physiological events precisely in immune modulation via chemokine receptors. The chemokine receptors are G-protein coupled receptors express mainly on the cell surface of immune cells. Retroviruses, including HIV in the early stage of infection, primarily target chemokines receptors and get internalized easily into immune cells; T cell and escape from immune surveillance. HIV glycoprotein selectively develops an affinity for the extracellular domain of chemokines receptors and allows the pathogen to internalize via CCR-5. Now, CCR-5 remains a crucial signaling pathway that can be translated into the therapeutic target by changing the receptor protein environment. Many populations have a mutation in coding and promoter regions of CCR-5, tuning a resistance for HIV infection. Natively, there are several mechanisms where the human genome remains in the dynamic state by changing its composition and acquiring variations. Single nucleotide polymorphism is spontaneous phenomenon responsible for precise and point mutation at the genome. Several studies have demonstrated that European and African American populations are enriched in significant CCR5 promoter SNP (CCR5Δ32) in the coding and promoter region as well. Now, such SNP can be an early-stage biomarker in studying HIV and other similar infections. Here, in this study, we have elucidated the role of SNP (both the promoter and coding region) and the fate of HIV infections. We also empathized with the genetics of such SNPs, mostly frequency and its immunological impact.
趋化因子是一类小蛋白质分子,通过趋化因子受体精确地参与各种生理事件,尤其是免疫调节。趋化因子受体是G蛋白偶联受体,主要表达于免疫细胞的细胞表面。逆转录病毒,包括感染早期的HIV,主要靶向趋化因子受体,并容易内化进入免疫细胞;T细胞从而逃避免疫监视。HIV糖蛋白选择性地与趋化因子受体的细胞外结构域产生亲和力,并使病原体通过CCR-5内化。现在,CCR-5仍然是一条关键的信号通路,通过改变受体蛋白环境可将其转化为治疗靶点。许多人群在CCR-5的编码区和启动子区存在突变,从而产生对HIV感染的抗性。自然地,人类基因组有几种机制可通过改变其组成和获得变异而保持动态状态。单核苷酸多态性是一种自发现象,负责基因组的精确点突变。多项研究表明,欧洲和非裔美国人在编码区和启动子区也富含显著的CCR5启动子单核苷酸多态性(CCR5Δ32)。现在,这种单核苷酸多态性可以作为研究HIV和其他类似感染的早期生物标志物。在此项研究中,我们阐明了单核苷酸多态性(启动子区和编码区)的作用以及HIV感染的转归。我们还着重研究了此类单核苷酸多态性的遗传学,主要是其频率及其免疫学影响。