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

八名患者的 HIV-1 基因随时间变化的模式

• 批准号: 2463687
• 负责人: C A WINKLER
• 金额: --
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2463687
• 关键词: HIV envelope protein; HIV infections; biochemical evolution; clinical research; complementary DNA; genetic mapping; genetic polymorphism; helper T lymphocyte; hemophilia As; human immunodeficiency virus 1; human tissue; immunogenetics; leukocyte count; nucleic acid sequence; polymerase chain reaction; virion; virus RNA; virus characteristic; virus genetics

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.

HIV-1变异在纵向系统发育分析中的检验 8例血友病儿童HIV env基因V3区基因突变 青少年。根据CD_4~+T细胞百分率选择患者。 血友病患者登记的头两年细胞数量下降 成长与发展研究。这一分析与以前的大多数不同 分析了血浆中HIV病毒RNA和非前病毒DNA的研究 潜伏期间病毒粒子多样性的范围和特征 无症状期通过CD4T细胞下降。主要预赛 研究结果是：(1)具有相似临床病程的人 明显不同程度的病毒多样性在 CD4T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 一名患者感染艾滋病毒，一名患者有巨噬细胞，另一名患者有 T细胞嗜性基因分型特征，在多个时间点共存 并以不同的进化速度被检测到。(3)正面 V3区域内氨基酸替换的选择与 处于免疫状态。在四名患者中，有三名患者出现了 CD4T细胞变化时阳性选择的总趋势 计数为200英镑，但在免疫压力下，突变往往是沉默的。 随着CD4T细胞计数降至200以下，这一数字有所下降。(4)来自 患者体内的多个时间点不会聚集在不同的位置 克拉兹。相反，发现时间点内序列与 其他时间点的序列。这表明早期的变种 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 监视系统。