South African National Bioinformatics Institute, University of the Western Cape, Private Bag X17, Belville, 7535, South Africa.
BMC Infect Dis. 2012 Sep 2;12:203. doi: 10.1186/1471-2334-12-203.
In human immunodeficiency virus type 1 (HIV-1) infection, transmitted viruses generally use the CCR5 chemokine receptor as a coreceptor for host cell entry. In more than 50% of subtype B infections, a switch in coreceptor tropism from CCR5- to CXCR4-use occurs during disease progression. Phenotypic or genotypic approaches can be used to test for the presence of CXCR4-using viral variants in an individual's viral population that would result in resistance to treatment with CCR5-antagonists. While genotyping approaches for coreceptor-tropism prediction in subtype B are well established and verified, they are less so for subtype C.
Here, using a dataset comprising V3 loop sequences from 349 CCR5-using and 56 CXCR4-using HIV-1 subtype C viruses we perform a comparative analysis of the predictive ability of 11 genotypic algorithms in their prediction of coreceptor tropism in subtype C. We calculate the sensitivity and specificity of each of the approaches as well as determining their overall accuracy. By separating the CXCR4-using viruses into CXCR4-exclusive (25 sequences) and dual-tropic (31 sequences) we evaluate the effect of the possible conflicting signal from dual-tropic viruses on the ability of a of the approaches to correctly predict coreceptor phenotype.
We determined that geno2pheno with a false positive rate of 5% is the best approach for predicting CXCR4-usage in subtype C sequences with an accuracy of 94% (89% sensitivity and 99% specificity). Contrary to what has been reported for subtype B, the optimal approaches for prediction of CXCR4-usage in sequence from viruses that use CXCR4 exclusively, also perform best at predicting CXCR4-use in dual-tropic viral variants.
The accuracy of genotyping approaches at correctly predicting the coreceptor usage of V3 sequences from subtype C viruses is very high. We suggest that genotyping approaches can be used to test for coreceptor tropism in HIV-1 group M subtype C with a high degree of confidence that they will identify CXCR4-usage in both CXCR4-exclusive and dual tropic variants.
在人类免疫缺陷病毒 1 型（HIV-1）感染中，传播的病毒通常使用 CCR5 趋化因子受体作为宿主细胞进入的辅助受体。在超过 50%的 B 亚型感染中，在疾病进展过程中会发生辅助受体嗜性从 CCR5 向 CXCR4 的转变。表型或基因型方法可用于检测个体病毒群体中存在的 CXCR4 利用病毒变异体，这将导致对 CCR5 拮抗剂治疗产生耐药性。虽然 B 亚型中用于辅助受体嗜性预测的基因分型方法已经得到很好的建立和验证，但对于 C 亚型则不然。
在这里，我们使用包含 349 个 CCR5 利用和 56 个 CXCR4 利用 HIV-1 C 亚型病毒的 V3 环序列的数据集，对 11 种基因型算法在 C 亚型中预测辅助受体嗜性的预测能力进行比较分析。我们计算了每种方法的敏感性和特异性，并确定了它们的整体准确性。通过将 CXCR4 利用病毒分为 CXCR4 特异性（25 个序列）和双嗜性（31 个序列），我们评估了来自双嗜性病毒的可能冲突信号对正确预测辅助受体表型的方法的能力的影响。
我们确定，假阳性率为 5%的 geno2pheno 是预测 C 亚型序列中 CXCR4 利用的最佳方法，准确率为 94%（89%的敏感性和 99%的特异性）。与 B 亚型报道的情况相反，在仅使用 CXCR4 的病毒的序列中预测 CXCR4 利用的最佳方法，在预测双嗜性病毒变异体中的 CXCR4 利用时也表现最佳。
基因型方法正确预测 C 亚型病毒 V3 序列辅助受体利用的准确性非常高。我们建议可以使用基因分型方法对 HIV-1 M 组 C 亚型中的辅助受体嗜性进行测试，具有高度信心可以识别 CXCR4 利用在 CXCR4 特异性和双嗜性变体中。
