Mihm S, Ennen J, Pessara U, Kurth R, Dröge W
Institute of Immunology and Genetics, German Cancer Research Center, Heidelberg.
AIDS. 1991 May;5(5):497-503. doi: 10.1097/00002030-199105000-00004.
HIV-1 proviral DNA contains two binding sites for the transcription factor NF-kappa B. HIV-1-infected individuals have, on average, abnormally high levels of tumour necrosis factor alpha (TNF alpha) and abnormally low plasma cysteine levels. We therefore investigated the effects of cysteine and related thiols on HIV-1 replication and NF-kappa B expression. The experiments in this report show that cysteine or N-acetylcysteine (NAC) raise the intracellular glutathione (GSH) level and inhibit HIV-1 replication in persistently infected Molt-4 and U937 cells. However, inhibition of HIV-1 replication appears not to be directly correlated with GSH levels. Cysteine and NAC also inhibit NF-kappa B activity as determined by electrophoretic mobility shift assays and chloramphenicol acetyl-transferase (CAT) gene expression under control of NF-kappa B binding sites in uninfected cells. This suggests that the cysteine deficiency in HIV-1-infected individuals may cause an over-expression of NF-kappa B-dependent genes and enhance HIV-1 replication. NAC may be considered for the treatment of HIV-1-infected individuals.
HIV-1前病毒DNA含有转录因子核因子κB（NF-κB）的两个结合位点。感染HIV-1的个体平均具有异常高水平的肿瘤坏死因子α（TNFα）和异常低的血浆半胱氨酸水平。因此，我们研究了半胱氨酸及相关硫醇对HIV-1复制和NF-κB表达的影响。本报告中的实验表明，半胱氨酸或N-乙酰半胱氨酸（NAC）可提高细胞内谷胱甘肽（GSH）水平，并抑制持续感染的Molt-4和U937细胞中的HIV-1复制。然而，HIV-1复制的抑制似乎与GSH水平没有直接关联。通过电泳迁移率变动分析以及在未感染细胞中NF-κB结合位点控制下的氯霉素乙酰转移酶（CAT）基因表达测定，半胱氨酸和NAC还可抑制NF-κB活性。这表明HIV-1感染个体中的半胱氨酸缺乏可能导致NF-κB依赖性基因的过度表达并增强HIV-1复制。NAC可考虑用于治疗HIV-1感染个体。
