MYCOBACTERIUM-TUBERCULOSIS ENHANCES HUMAN IMMUNODEFICIENCY VIRUS-1 REPLICATION BY TRANSCRIPTIONAL ACTIVATION AT THE LONG TERMINAL REPEAT
MYCOBACTERIUM-TUBERCULOSIS ENHANCES HUMAN IMMUNODEFICIENCY VIRUS-1 REPLICATION BY TRANSCRIPTIONAL ACTIVATION AT THE LONG TERMINAL REPEAT
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DOI：
10.1172/jci117924
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发表时间：
1995-05-01
影响因子：
15.9
通讯作者：
ROM, WN
中科院分区：
文献类型：
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作者：
ZHANG, YH;NAKATA, K;ROM, WN
结核病已成为一种流行病，由大量感染人类免疫缺陷病毒的个体，特别是那些注射毒品使用者所推动。我们发现，在3例HIV阳性患者中，结核分枝杆菌感染相关部位支气管肺泡灌洗液中p24水平显著升高，从4倍增加到208倍。我们使用体外细胞培养模型来确定结核病是否可以激活HIV-1的复制。体外感染HIV-1（JR-CSF）的单核吞噬细胞系U937和THP-1，用活M.结核杆菌H37 Ra的p24在培养上清液中增加了三倍。使用HTV-1长末端重复与氯霉素乙酰转移酶（CAT）报告构建体，活M，结核病增加转录20倍，在THP-1细胞，细胞壁成分刺激CAT的表达在较小程度上。核因子-κ B增强子元件是导致CAT活性增加的主要原因，尽管两个上游核因子-IL 6位点也可能有助于增强转录。结核病从21倍下降到8倍。结核分枝杆菌对HIV-1复制的刺激可能会加剧双重感染个体的宿主免疫应答功能障碍。
Tuberculosis has emerged as an epidemic fueled by the large number of individuals infected with the human immunodeficiency virus, especially those who are injecting drug users. We found a striking increase from 4- to 208-fold in p24 levels in bronchoalveolar lavage fluid from involved sites of Mycobacterium tuberculosis infection vs uninvolved sites in three HIV+ patients. We used an in vitro cell culture model to determine if tuberculosis could activate replication of HIV-1. Mononuclear phagocyte cell lines U937 and THP-1 infected with HIV-1(JR-CSF), in vitro and stimulated with live M. tuberculosis H37Ra, had a threefold increase in p24 in culture supernatants. Using the HTV-1 long terminal repeat with a chloramphenicol acetyltransferase (CAT) reporter construct, live M, tuberculosis increased transcription 20-fold in THP-1 cells, and cell wall components stimulated CAT expression to a lesser extent. The nuclear factor-kappa B enhancer element was responsible for the majority of the increased CAT activity although two upstream nuclear factor-IL6 sites may also contribute to enhanced transcription, Antibodies to TNF-alpha and IL-1 inhibited the increase in CAT activity of the HIV-1 long terminal repeat by M. tuberculosis from 21-fold to 8-fold. Stimulation of HIV-1 replication by M, tuberculosis may exacerbate dysfunction of the host immune response in dually infected individuals.