Baier-Bitterlich G, Fuchs D, Zangerle R, Baeuerle P A, Werner E R, Fresser F, Uberall F, Baier G, Wachter H
Institute for Medical Chemistry and Biochemistry, University of Innsbruck, Austria.
AIDS Res Hum Retroviruses. 1997 Jan 20;13(2):173-8. doi: 10.1089/aid.1997.13.173.
Infection with human immunodeficiency virus type 1 and 2 is associated with elevated concentrations of neopterin, released in large quantities by human macrophages on stimulation with interferon gamma. Evidence has suggested a potential role of neopterin derivatives in oxygen radical-mediated processes. Here we show that the redox-sensitive transcription factors AP-1 and NF-kappaB are activated by 7,8-dihydroneopterin, either directly (AP-1), or by the synergistic action with tumor necrosis factor alpha (NF-kappaB). We could further demonstrate that 7,8-dihydroneopterin enhances HIV-1 expression as shown in transient transfection assays using HIV-1 CAT promoter-reporter gene constructs. In sera of HIV+ patients 7,8-dihydroneopterin significantly correlated with neopterin and HIV-1 p24 antigen. On the basis of our data we therefore assume that 7,8-dihydroneopterin might augment progression to higher stages of HIV-associated disease.
感染1型和2型人类免疫缺陷病毒与新蝶呤浓度升高有关，新蝶呤是人类巨噬细胞在受到γ干扰素刺激后大量释放的。有证据表明新蝶呤衍生物在氧自由基介导的过程中具有潜在作用。在此我们表明，氧化还原敏感转录因子AP-1和NF-κB可被7,8-二氢新蝶呤激活，AP-1是直接激活，而NF-κB是通过与肿瘤坏死因子α协同作用激活。我们还能进一步证明，如使用HIV-1 CAT启动子-报告基因构建体进行的瞬时转染试验所示，7,8-二氢新蝶呤可增强HIV-1表达。在HIV阳性患者的血清中，7,8-二氢新蝶呤与新蝶呤及HIV-1 p24抗原显著相关。基于我们的数据，因此我们推测7,8-二氢新蝶呤可能会加速HIV相关疾病进展至更高阶段。
