HIV-1 GENETIC VARIATION IN INFECTED HEMOPHILIACS OVER TIME

感染HIV-1后， 潜伏期、宿主免疫反应和CD 4+细胞率 T细胞减少 观察到的变异性的三个可能原因 HIV-1感染的结果可能是其他病毒、宿主等辅因子 基因差异和HIV-1病毒群内的变异。 的目标 本项目旨在分析HIV-1序列的范围和模式， 在四个稳定的非进展者中， 和四个CD 4 T细胞计数下降超过75%的快速进展者 入组血友病生长研究后的前24个月内 发展研究。 该研究比较了定量和 随着时间的推移，这两种病毒之间的病毒序列存在定性差异 通过使用巢式聚合酶链反应（PCR）， 从通过以下方法获得的cDNA扩增env、gag、pol和nef的选定区域 血浆病毒体RNA、DNA的逆转录酶PCR 原病毒和病毒分离物。 病毒序列的PCR产物 （从外周血单核细胞、血浆和分离株中获得） 并将来自每个患者的核苷酸序列从基线 通过七次访问进行比较。 迄今取得的进展包括： 克隆的成功测序和初步系统发育分析 在V3的7个时间点，来自两个快速和两个缓慢进展者 环境的循环

Following infection by HIV-1, there is considerable variation in duration of the latency period, host immunological response, and the rate of CD4 T-cell decline. Three possible causes of the variability observed in outcome to HIV-1 infection may be cofactors such as other viruses, host genetic differences, and variants within the HIV-1 swarm. The goal of this project is to analyze the extent and pattern of HIV-1 sequence divergence over the course of infection in four stable, non-progressors and four rapid progressors whose CD4 T-cell count declined more than 75% in the first 24 months following enrollment into the Hemophilia Growth and Development Study. The study is comparing the quantitative and qualitative differences over time in viral sequences between these two dichotomous groups by using nested polymerase chain reaction (PCR) to amplify selected regions of env, gag, pol, and nef from cDNA obtained by reverse transcriptase PCR of plasma virion RNA, DNA from integrated provirus, and virus isolates. The PCR products of viral sequences (obtained from peripheral mononuclear blood cells, plasma, and isolates) are cloned and the nucleotide sequences from each patient from baseline through visit seven are compared. Progress to date includes the successful sequencing and preliminary phylogenetic analysis of clones from two fast and two slow progressors at seven time points for the V3 loop of the env.