PATTERNS OF HIV-1 GENETIC VARIATION OVER TIME IN EIGHT PATIENTS

在纵向系统发育分析中检查HIV-1变异 8例血友病患儿HIV env基因V3区的表达， 青少年。 根据CD 4 T细胞比率选择患者， 血友病患者入组前两年的细胞下降 生长发育研究。 这一分析不同于以往的大多数分析。 研究中，分析了血浆HIV病毒RNA，而不是前病毒DNA， 在潜伏期内病毒体多样性的程度和特征 无症状期通过CD 4 T细胞下降。 重大前期 结果发现：（1）具有相似临床病程的个体 不同时期病毒多样性水平的差异 CD 4 T细胞下降，表明不同的免疫压力 准物种进化的速度。 (2)两个不同的种群 艾滋病毒在一个单一的病人，一个与巨噬细胞-和其他 嗜T细胞基因型特征，在多个时间点共存 和不同的进化速率。 (3)积极 V3区内氨基酸取代的选择与 免疫状态良好。 在四个病人中的三个， 当CD 4 T细胞 计数>200，但当免疫压力 随着CD 4 T细胞计数下降到200以下。 (4)序列从 患者内的多个时间点没有聚集在不同的 进化枝 相反，发现时间点内序列与 其他时间点的序列。 这表明早期的变异 随着时间的推移持续存在，可能代表逃避免疫的逃逸突变体， 监视

HIV-1 variation was examined in a longitudinal phylogenetic analysis of the V3 region of the HIV env gene in 8 hemophiliac children and adolescents. The patients were selected based on the rate of CD4 T- cell decline during the first two years of enrollment in the Hemophilia Growth and Development Study. The analysis differs from most previous studies in that plasma HIV viral RNA and not proviral DNA was analyzed for the extent and character of virion diversity during the latent asymptomatic period through CD4 T-cell decline. Major preliminary findings are: (1) Individuals with similar clinical courses have distinctively different levels of viral diversity during the period of CD4 T-cell decline, suggesting differential immune pressures driving the rate of quasispecies evolution. (2) Two divergent populations of HIV in a single patient, one with macrophage- and the other T-cell-tropic genotypic features, co-existing over multiple timepoints and with different rates of evolution were detected. (3) Positive selection for amino acid substitution within the V3 region correlates well with immune status. In three of the four patients, there was a general trend towards positive selection for change when CD4 T-cell counts were >200, but mutations tend to be silent when immune pressure decreased as CD4 T-cell counts fell below 200. (4) Sequences from multiple timepoints within a patient did not cluster in distinct clades. Instead intra-timepoint sequences were found to overlap with sequences from other timepoints. This suggests that early variants persist over time and may represent escape mutants that evaded immune surveillance.