Evidence for limited genetic compartmentalization of HIV-1 between lung and blood.
Evidence for limited genetic compartmentalization of HIV-1 between lung and blood.
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DOI：
10.1371/journal.pone.0006949
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发表时间：
2009-09-14
期刊：
影响因子：
3.7
通讯作者：
Mittler JE
中科院分区：
文献类型：
--
作者：
Heath L;Fox A;McClure J;Diem K;van 't Wout AB;Zhao H;Park DR;Schouten JT;Twigg HL;Corey L;Mullins JI;Mittler JE
HIV-1经常在感染者的肺部检测到，可能在肺部机会性感染的发展中很重要。独特的肺环境，丰富的肺泡巨噬细胞和特殊的局部免疫反应，可能有助于差异进化或选择HIV-1。我们将肺中的HIV-1与同期血液中的病毒群联系起来。对18名受试者的配对肺（诱导痰或支气管肺泡灌洗液）和血液（已分选或未分选PBMC的血浆RNA和前病毒DNA）进行了HIV-1 env的C2-V5区测序。使用5种已建立的树或基于距离的方法评估组织对之间的区隔性，包括排列测试以确定统计显著性。我们在10/18个受试者中发现肺和血液的区隔性的统计证据，尽管在所有受试者的系统发育树上肺和血液序列是混杂的。显示最大区隔化的受试者在BAL样本中包含许多几乎相同的序列，这表明克隆扩增可能有助于在某些情况下降低肺中的病毒多样性。然而，肺中的HIV-1序列总体上并不均匀，我们也无法在V3中找到与巨噬细胞嗜性相关的肺特异性基因型。在血液中发现预测X4基因型的所有四名受试者中，肺中也发现了预测X4基因型。我们的研究结果支持HIV-1在循环血液和肺组织之间持续迁移的图景，可能是非常有限程度的局部进化或克隆复制。
HIV-1 is frequently detected in the lungs of infected individuals and is likely important in the development of pulmonary opportunistic infections. The unique environment of the lung, rich in alveolar macrophages and with specialized local immune responses, may contribute to differential evolution or selection of HIV-1. We characterized HIV-1 in the lung in relation to contemporaneous viral populations in the blood. The C2-V5 region of HIV-1 env was sequenced from paired lung (induced sputum or bronchoalveolar lavage) and blood (plasma RNA and proviral DNA from sorted or unsorted PBMC) from 18 subjects. Compartmentalization between tissue pairs was assessed using 5 established tree or distance-based methods, including permutation tests to determine statistical significance. We found statistical evidence of compartmentalization between lung and blood in 10/18 subjects, although lung and blood sequences were intermingled on phylogenetic trees in all subjects. The subject showing the greatest compartmentalization contained many nearly identical sequences in BAL sample, suggesting clonal expansion may contribute to reduced viral diversity in the lung in some cases. However, HIV-1 sequences in lung were not more homogeneous overall, nor were we able to find a lung-specific genotype associated with macrophage tropism in V3. In all four subjects in whom predicted X4 genotypes were found in blood, predicted X4 genotypes were also found in lung. Our results support a picture of continuous migration of HIV-1 between circulating blood and lung tissue, with perhaps a very limited degree of localized evolution or clonal replication.
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DOI：
10.1097/00126334-200008150-00002
发表时间：
2000-08-15
期刊：
JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
影响因子：
--
作者：
Collins, KR;Mayanja-Kizza, H;Arts, EJ
通讯作者：
Arts, EJ
影响因子：
5.4
作者：
Liu, SL;Schacker, T;Mullins, JI
通讯作者：
Mullins, JI
影响因子：
6.8
作者：
AKAIKE, H
通讯作者：
AKAIKE, H
影响因子：
5.8
作者：
Deng, Wenjie;Nickle, David C.;Mullins, James I.
通讯作者：
Mullins, James I.
影响因子：
1.5
作者：
Diem, Kurt;Nickle, David C.;Krieger, John N.
通讯作者：
Krieger, John N.