Nakata K, Rom W N, Honda Y, Condos R, Kanegasaki S, Cao Y, Weiden M
Division of Pulmonary and Critical Care Medicine, New York University Medical Center, New York, USA.
Am J Respir Crit Care Med. 1997 Mar;155(3):996-1003. doi: 10.1164/ajrccm.155.3.9117038.
We investigated the in vivo effect of coinfection of Mycobacterium tuberculosis on human immunodeficiency virus type 1 (HIV-1) replication using bronchoalveolar lavage (BAL) of 11 HIV-1-infected patients with pulmonary tuberculosis and 10 patients with no lung disease. Lung segments involved with pulmonary tuberculosis had significantly elevated HIV-1 branched DNA (bDNA) levels and p24 in BAL compared with lung segments uninvolved with tuberculosis or with BAL from patients with no lung disease. The BAL viral burden was higher than plasma HIV-1 in tuberculosis patients, indicating local production of virus. BAL HIV-1 bDNA declined over the course of treatment for tuberculosis in three patients who underwent serial bronchoscopies. Tumor necrosis factor-alpha (TNF-alpha) and HIV-1 bDNA particles were strongly correlated (r2 = 0.9, p < 0.01) in lung segments involved with tuberculosis. The deduced amino acid sequence of HIV-1 gp120 V3 region from involved segments of three patients with pulmonary tuberculosis showed basic substitutions associated with altered viral phenotype. Phylogenetic analysis of V3 sequences demonstrated that BAL HIV-1 RNA had diverged from plasma. These data support the conclusion that pulmonary tuberculosis enhances local HIV-1 replication in vivo.
我们利用11例合并肺结核的HIV-1感染患者及10例无肺部疾病患者的支气管肺泡灌洗(BAL)样本,研究了结核分枝杆菌合并感染对1型人类免疫缺陷病毒(HIV-1)复制的体内影响。与未患结核病的肺段或无肺部疾病患者的BAL样本相比,合并肺结核的肺段中HIV-1分支DNA(bDNA)水平及p24水平显著升高。结核病患者的BAL病毒载量高于血浆HIV-1,表明病毒在局部产生。在接受系列支气管镜检查的3例患者中,BAL HIV-1 bDNA在结核病治疗过程中有所下降。在合并结核病的肺段中,肿瘤坏死因子-α(TNF-α)与HIV-1 bDNA颗粒高度相关(r2 = 0.9,p < 0.01)。3例肺结核患者受累肺段HIV-1 gp120 V3区推导的氨基酸序列显示出与病毒表型改变相关的碱性取代。V3序列的系统发育分析表明,BAL HIV-1 RNA与血浆中的RNA已发生分化。这些数据支持肺结核在体内增强局部HIV-1复制这一结论。