Chaudhary Omkar, Rajsekar Kavitha, Ahmed Imran, Verma Romsha, Bala Manju, Bhasin Rama, Luthra Kalpana
Department of Biochemistry, Room No. 3002, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.
J Clin Virol. 2008 Oct;43(2):196-201. doi: 10.1016/j.jcv.2008.06.005. Epub 2008 Sep 4.
A single nucleotide polymorphism (SNP) in SDF-1, the natural ligand for the HIV-1 coreceptor CXCR4, is implicated to have protective effects against HIV-1 infection. Dendritic cells are the first to encounter HIV-1 at mucosal sites and virus binding occurs via receptors known as DC-SIGN. Variations in the number of repeats in the neck region of DC-SIGN and DC-SIGNR are reported to possibly influence host susceptibility to HIV-1 infection. We examined the SNP of SDF1-3'A by PCR-restriction fragment length polymorphism (RFLP) and repeat region polymorphisms in DC-SIGN and DC SIGNR by PCR in healthy HIV seronegative individuals, high risk STD patients seronegative for HIV, and HIV-1 seropositive patients from northern India. The detected polymorphisms were confirmed by cloning and sequencing. The genotypic frequency of SDF1-3'A/SDF1-3'A in the 100 HIV-seronegative healthy individuals, 150 HIV seronegative STD patients, and 100 HIV-1 seropositive patients were 4%, 18% and 7%, respectively. A significantly higher frequency of SDF1-3'A/SDF1-3'A was observed in high risk STD patients as compared to HIV seropositive (p=0.014) and healthy HIV-1 seronegative tested individuals (p=0.001), suggesting a protective role of SDF1-3'A in HIV-1 infection. DC-SIGN polymorphism was rare and genotype 7/7 was predominant in all groups studied. DC-SIGNR was highly polymorphic and 11 genotypes were observed among the different study groups. The precise role of the polymorphic variants of DC-SIGNR needs to be elucidated in the population.
SDF-1是HIV-1共受体CXCR4的天然配体，其单核苷酸多态性（SNP）被认为对HIV-1感染具有保护作用。树突状细胞是在黏膜部位最先接触HIV-1的细胞，病毒通过名为DC-SIGN的受体发生结合。据报道，DC-SIGN和DC-SIGNR颈部区域重复序列数量的变化可能会影响宿主对HIV-1感染的易感性。我们通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）检测了健康的HIV血清阴性个体、HIV血清阴性的高危性传播疾病（STD）患者以及印度北部的HIV-1血清阳性患者中SDF1-3'A的SNP，并通过PCR检测了DC-SIGN和DC-SIGNR中的重复区域多态性。通过克隆和测序对检测到的多态性进行了确认。在100名HIV血清阴性的健康个体、150名HIV血清阴性的STD患者和100名HIV-1血清阳性患者中，SDF1-3'A/SDF1-3'A的基因型频率分别为4%、18%和7%。与HIV血清阳性患者（p=0.014）和健康的HIV-1血清阴性检测个体（p=0.001）相比，高危STD患者中SDF1-3'A/SDF1-3'A的频率显著更高，这表明SDF1-3'A在HIV-1感染中具有保护作用。DC-SIGN多态性罕见，在所有研究组中基因型7/7占主导地位。DC-SIGNR具有高度多态性，在不同研究组中观察到11种基因型。DC-SIGNR多态性变体在人群中的具体作用有待阐明。
