Greater diversity of HIV-1 quasispecies in HIV-infected individuals with active tuberculosis
Greater diversity of HIV-1 quasispecies in HIV-infected individuals with active tuberculosis
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DOI：
10.1097/00126334-200008150-00002
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发表时间：
2000-08-15
期刊：
影响因子：
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通讯作者：
Arts, EJ
中科院分区：
文献类型：
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作者：
Collins, KR;Mayanja-Kizza, H;Arts, EJ
目的：患者体内 HIV-1 异质性的持续增加被认为有助于逃避宿主免疫反应并最终发展为艾滋病。结核病 (TB) 在 HIV-1 疾病过程中的早期和晚期均被诊断出来，并且可能通过激活 HIV-1 免疫反应和增加 HIV-1 复制来增加 HIV-1 准种的多样性。我们检查了 HIV-1 感染的结核病患者中的 HIV-1 异质性是否发生改变。方法：从乌干达坎帕拉的 7 名 HIV-1 感染活动性结核病患者（HIV/TB 患者）和 9 名 HIV-1 感染患者（HIV 患者）中获取血液样本（CD4 计数为 0-650 个细胞/mu1，HIV 借出为 700-750.000 RNA 拷贝/mi）。通过巢式聚合酶链式反应(PCR)从每位患者裂解的外周血单核细胞(PBMC)中扩增HIV-1包膜基因(env)的C2-C3区域，然后进行测序。克隆准特异性分析和异源双链追踪分析 (HTA)。结果：与 HIV 组相比，HIV/TB 个体中 env DNA 片段的 HTA 显示异质性增加。对每个患者的十个单独的env克隆的进一步序列和HTA分析表明，HIV/TB患者中的HIV突变频率显着高于HIV患者。 结论：HIV-1异质性的增加可能与TB介导的HIV-1复制的增加有关。然而，HIV/TB 患者中的 HIV-1 准种群体多样化，而不是 MV 患者中的紧密准种簇，这表明肺源性 HIV-1 分离株可能从受结核病影响的器官中传播。
Objective: A continual increase in intrapatient HIV-1 heterogeneity is thought to contribute to evasion of host immune response and eventual progression to AIDS. Tuberculosis (TB) is diagnosed both early and late during the course of HIV-1 disease and may increase diversity of HIV-1 quasispecies by activating the HIV-1 immune response and increasing HIV-1 replication. We examined whether HIV-1 heterogeneity is altered in HIV-l-infected individuals with TB.Methods: Blood samples were obtained from 7 HIV-1-infected patients with active TB (HIV/TB patients) and 9 HIV-1-infected patients (HIV patients) in Kampala, Uganda (CD4 counts of 0-650 cells/mu1 and HIV lends of 700-750.000 RNA copies/ mi). The C2-C3 region of the HIV-I envelope gene (env) was amplified by nested polymerase chain reaction (PCR) from lysed peripheral blood mononuclear cells (PBMCs) of each patient, and then subject to sequencing. clonal-quasispecics analysis and heteroduplex tracking analysis (HTA).Results: HTA of env DNA fragments showed increased heterogeneity in the HIV/ TB individuals compared with the HIV group. Further sequence and HTA analysis on ten individual env clones for each patient showed significantly greater HIV mutation Frequencies in HIV/TB patients than in HIV patients.Conclusion: An increase in HIV-I heterogeneity may be associated with a TB-mediated increase in HIV-I replication. However, a diverse HIV-1 quasispecies population in HIV/TB patients as opposed to tight quasispecies clusters in MV patients suggests a possible dissemination of lung-derived HIV-1 isolates from the TB-affected organ.