Jiaxing Key Laboratory of Pathogenic Microbiology,Jiaxing Municipal Centre for Disease Control and Prevention,No.486, Wenqiao Road,Jiaxing, 314001,China.
Institute of AIDS Control and Prevention, Zhejiang Provincial Centre for Disease Control and Prevention,No.3399, Binsheng Road,Hangzhou, 310051,China.
Epidemiol Infect. 2019 Jan;147:e181. doi: 10.1017/S0950268819000700.
Co-receptor tropism has been identified to correlate with HIV-1 transmission and the disease progression in patients. A molecular epidemiology investigation of co-receptor tropism is important for clinical practice and effective control of HIV-1. In this study, we investigated the co-receptor tropism on HIV-1 variants of 85 antiretroviral-naive patients with Geno2pheno algorithm at a false-positive rate of 10%. Our data showed that a majority of the subjects harboured the CCR5-tropic virus (81.2%, 69/85). No significant differences in gender, age, baseline CD4+ T-cell counts and transmission routes were observed between subjects infected with CXCR4-tropic or CCR5-tropic virus. The co-receptor tropism appeared to be associated with the virus genotype; a significantly more CXCR4-use was predicted in CRF01_AE infections whereas all CRF07_BC and CRF08_BC were predicted to use CCR5 co-receptor. Sequences analysis of V3 revealed a higher median net charge in the CXCR4 viruses over CCR5 viruses (4.0 vs. 3.0, P < 0.05). The predicted N-linked glycosylation site between amino acids 6 and 8 in the V3 region was conserved in CCR5 viruses, but not in CXCR4 viruses. Besides, variable crown motifs were observed in both CCR5 and CXCR4 viruses, of which the most prevalent motif GPGQ existed in both viral tropism and almost all genotypes identified in this study except subtype B. These findings may offer important implications for clinical practice and enhance our understanding of HIV-1 biology.
共受体嗜性已被确定与 HIV-1 的传播和患者的疾病进展相关。对共受体嗜性进行分子流行病学调查对于临床实践和有效控制 HIV-1 非常重要。在这项研究中，我们使用 Geno2pheno 算法以 10%的假阳性率对 85 名未接受过抗逆转录病毒治疗的患者的 HIV-1 变异体的共受体嗜性进行了研究。我们的数据显示，大多数患者携带 CCR5 嗜性病毒（81.2%，69/85）。感染 CXCR4 嗜性或 CCR5 嗜性病毒的患者在性别、年龄、基线 CD4+T 细胞计数和传播途径方面无显著差异。共受体嗜性似乎与病毒基因型有关；在 CRF01_AE 感染中，预测 CXCR4 使用的比例显著更高，而所有 CRF07_BC 和 CRF08_BC 均预测使用 CCR5 共受体。V3 区序列分析显示，CXCR4 病毒的中位净电荷高于 CCR5 病毒（4.0 对 3.0，P < 0.05）。V3 区氨基酸 6 和 8 之间预测的 N-连接糖基化位点在 CCR5 病毒中保守，但在 CXCR4 病毒中不存在。此外，在 CCR5 和 CXCR4 病毒中均观察到可变冠群基序，其中最常见的基序 GPGQ 存在于这两种病毒嗜性中，并且几乎存在于本研究鉴定的所有基因型中，除了 B 亚型。这些发现可能为临床实践提供重要意义，并增强我们对 HIV-1 生物学的理解。
