Ha H C, Juluri K, Zhou Y, Leung S, Hermankova M, Snyder S H
Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3364-8. doi: 10.1073/pnas.051633498. Epub 2001 Mar 6.
Poly(ADP-ribose) polymerase-1 (PARP-1; EC ) is an abundant nuclear enzyme, activated by DNA strand breaks to attach up to 200 ADP-ribose groups to nuclear proteins. As retroviral infection requires integrase-catalyzed DNA strand breaks, we examined infection of pseudotyped HIV type I in fibroblasts from mice with a targeted deletion of PARP-1. Viral infection is almost totally abolished in PARP-1 knockout fibroblasts. This protection from infection reflects prevention of viral integration into the host genome. These findings suggest a potential for PARP inhibitors in therapy of HIV type I infection.
聚(ADP-核糖)聚合酶-1(PARP-1;EC )是一种丰富的核酶,被DNA链断裂激活后可将多达200个ADP-核糖基团连接到核蛋白上。由于逆转录病毒感染需要整合酶催化的DNA链断裂,我们检测了在PARP-1靶向缺失的小鼠成纤维细胞中I型假型HIV的感染情况。在PARP-1基因敲除的成纤维细胞中,病毒感染几乎完全被消除。这种对感染的保护作用反映了病毒整合到宿主基因组的过程被阻止。这些发现提示PARP抑制剂在治疗I型HIV感染方面具有潜力。