Longitudinal analysis of simian immunodeficiency virus (SIV) replication in the lungs: Compartmentalized regulation of SIV
Longitudinal analysis of simian immunodeficiency virus (SIV) replication in the lungs: Compartmentalized regulation of SIV
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DOI：
10.1086/507429
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发表时间：
2006-10-01
影响因子：
6.4
通讯作者：
Clements, Janice E.
中科院分区：
文献类型：
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作者：
Barber, Sheila A.;Gama, Lucio;Clements, Janice E.
背景在艾滋病发病前，人类免疫缺陷病毒（HIV）和猿猴免疫缺陷病毒（SIV）在肺部的复制被认为是潜伏的。病毒复制何时以及如何在肺部受到控制尚不清楚。在本研究中，我们在一个全面的，纵向分析的SIV/猕猴模型中，研究了肺和从支气管肺泡灌洗（BAL）样品中回收的细胞中的病毒复制。通过聚合酶链反应（PCR）和实时逆转录PCR（RT-PCR）定量基因特异性RNA和DNA。使用Dynabeads CD 14（Invitrogen）分离肺泡巨噬细胞。通过Western blot分析检测CCAAT/增强子结合蛋白β（C/EBP β）亚型的表达。SIV复制发生在肺部急性感染，并与血浆病毒载量相关。在这个时候，诱导涉及干扰素-β和C/EBPb的显性阴性亚型的先天免疫应答。SIV RNA表达在无症状感染期间在肺中被抑制，当与血浆病毒载量不存在相关性时，直到SIV RNA水平在晚期疾病期间再次反弹。BAL细胞中病毒RNA水平的调节反映了整个感染阶段肺组织中的RNA水平。BAL细胞中SIV RNA的定量提供了肺组织中病毒复制的一致替代评估。先天性免疫应答有助于肺中急性SIV复制的区室化抑制。
Background. Before the onset of AIDS, replication of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) in the lungs is considered to be latent. When and how virus replication is controlled in the lungs is unclear. In the present study, we examine virus replication in the lungs and in cells recovered from bronchoalveolar lavage (BAL) samples in a comprehensive, longitudinal analysis of an SIV/macaque model.Methods. Gene-specific RNA and DNA were quantitated by polymerase chain reaction (PCR) and by real-time reverse-transcription PCR (RT-PCR). Alveolar macrophages were isolated using Dynabeads CD14 (Invitrogen). Expression of CCAAT/enhancer-binding protein beta (C/EBP beta) isoforms was examined by Western blot analysis.Results. SIV replication occurred in the lungs during acute infection and correlated with plasma viral load. Innate immune responses involving interferon-beta and the dominant-negative isoform of C/EBPb were induced at this time. SIV RNA expression was suppressed in the lungs during asymptomatic infection, when no correlation existed with plasma viral load until SIV RNA levels rebounded again during late-stage disease. Modulation of viral RNA levels in BAL cells reflected RNA levels in lung tissue throughout each phase of infection.Conclusion. Quantitation of SIV RNA in BAL cells provides a consistent surrogate assessment of virus replication in lung tissue. Innate immune responses contribute to compartmentalized suppression of acute SIV replication in the lungs.