Institute for Medical Virology, Hospital of Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
Med Microbiol Immunol. 2010 Nov;199(4):323-32. doi: 10.1007/s00430-010-0167-9. Epub 2010 Aug 10.
The evolution of intra-host human immunodeficiency virus type 1 (HIV-1) quasispecies prior and after treating active tuberculosis (TB) with chemotherapy in HIV-1/TB patients was assessed. Two time points HIV-1 quasispecies were evaluated by comparing HIV-1-infected patients with active tuberculosis (HIV-1/TB) and HIV-1-infected patients without tuberculosis (HIV-1/non-TB). Plasma samples were obtained from the Frankfurt HIV cohort, and HIV-1 RNA was isolated. C2V5 env was amplified by PCR and molecular cloning was performed. Eight to twenty-five clones were sequenced from each patient. Various phylogenetic analyses were performed. We found a significant increase in diversity and divergence in HIV-1/TB compared to the HIV-1/non-TB. For HIV-1/TB, the average rate of evolution of C2V5 env was higher than previous reports (2.4 × 10(-4) substitution/site/day). Two groups of HIV-1/TB were observed based on the rate of HIV-1 evolution and coreceptor usage: A fast evolving R5-tropic dominating group and a relatively slowly evolving X4 group. The results demonstrated that active TB has an impact on HIV-1 viral diversity and divergence over time. The influence of active TB on longitudinal evolution of HIV-1 may be predominant for R5 viruses.
本研究旨在评估人类免疫缺陷病毒 1 型(HIV-1)感染者在接受抗结核化疗前后,体内病毒准种的演变。通过比较合并活动性肺结核(HIV-1/TB)和不合并肺结核(HIV-1/非 TB)的 HIV-1 感染者,评估了 HIV-1/TB 患者治疗前和治疗后 HIV-1 准种的演变。从法兰克福 HIV 队列中采集血浆样本,并提取 HIV-1 RNA。采用 PCR 扩增 C2V5 区 env 基因,并进行分子克隆。从每位患者中选取 8-25 个克隆进行测序。进行了各种系统发生分析。结果显示,与 HIV-1/非 TB 患者相比,HIV-1/TB 患者的 HIV-1 多样性和差异显著增加。对于 HIV-1/TB 患者,C2V5 env 区的平均进化率高于以往的报告(2.4×10-4 个替换/位点/天)。根据 HIV-1 的进化率和辅助受体使用情况,HIV-1/TB 患者可分为两组:快速进化的 R5 嗜性主导组和相对缓慢进化的 X4 组。研究结果表明,活动性肺结核会影响 HIV-1 病毒的多样性和随时间的变化。对于 R5 病毒,活动性肺结核对 HIV-1 纵向进化的影响可能占主导地位。