Laboratory of Virology, Clinical Department, National Institute of Infectious Diseases INMI, Lazzaro Spallanzani, Italy.
AIDS. 2011 Mar 13;25(5):611-7. doi: 10.1097/QAD.0b013e328343489e.
HIV-1 V3 quasispecies was analyzed by ultra-deep pyrosequencing, in early HIV-infected patients, to assess possible correlations between quasispecies diversity, frequency of variants predicted to use CXCR4 and need for early antiretroviral treatment.
Twenty patients were retrospectively enrolled: 10 patients (group A) required HAART within 6 months from seroconversion and 10 (group B) remained free of therapy during this period. V3 quasispecies was assessed on plasma viral RNA and in peripheral blood mononuclear cell-associated proviral DNA. Prediction of coreceptor usage was performed by position-specific score matrix analysis.
Variants predicted to use CXCR4 were detected (frequency ≥0.3%) in the plasma of 50% of early infected patients (60% from group A and 40% from group B). Intrapatient frequency of these variants was highly variable (0.3-56.3%). A positive correlation was observed between the proportion of X4 variants and intrapatient quasispecies diversity. Quasispecies diversity and absolute numbers of X4 variants were significantly higher in patients from group A. The analysis of proviral DNA quasispecies, performed in a subgroup of five patients, showed that X4 variants were not detected in patients with RNA frequency below 0.3%, and detected at 3.6% in the patient with 56.3% of X4 plasma variants.
Our findings show that X4 variants may be frequently found, at variable intrapatient frequency, in early infected patients, and that quasispecies diversity and absolute numbers of X4 variants are significantly higher in patients undergoing early antiretroviral treatment. Further studies are mandatory to explore the clinical relevance of X4 variants present during early infection with respect to clinical progression and possible therapeutic implications.
通过超深度焦磷酸测序分析 HIV-1 V3 准种，以评估早期 HIV 感染者中准种多样性、预测使用 CXCR4 的变异体频率与早期抗逆转录病毒治疗需求之间的可能相关性。
回顾性纳入 20 例患者：10 例（A 组）患者在血清转换后 6 个月内需要接受 HAART，10 例（B 组）在此期间未接受治疗。在血浆病毒 RNA 和外周血单个核细胞相关前病毒 DNA 上评估 V3 准种。通过位置特异性评分矩阵分析预测辅助受体的使用。
50%的早期感染患者（A 组 60%，B 组 40%）的血浆中检测到预测使用 CXCR4 的变异体（频率≥0.3%）。这些变异体的个体内频率变化很大（0.3-56.3%）。观察到 X4 变异体的比例与个体内准种多样性之间存在正相关。A 组患者的准种多样性和 X4 变异体的绝对数量显著更高。对 5 例患者的前病毒 DNA 准种分析显示，RNA 频率低于 0.3%的患者中未检测到 X4 变异体，而在 X4 血浆变异体比例为 56.3%的患者中检测到 3.6%的 X4 变异体。
我们的研究结果表明，在早期感染患者中，X4 变异体可能以不同的个体内频率频繁出现，并且在接受早期抗逆转录病毒治疗的患者中，X4 变异体的准种多样性和绝对数量显著更高。需要进一步研究以探索早期感染时存在的 X4 变异体与临床进展和可能的治疗意义相关的临床相关性。
