Poly(ADP-ribose) polymerase-1 is required for efficient HIV-1 integration

Poly(ADP-ribose) polymerase-1 is required for efficient HIV-1 integration
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DOI:
10.1073/pnas.051633498
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发表时间:
2001-03-13
影响因子:
11.1
通讯作者:
Snyder, SH
Snyder, SH
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Ha, HC;Juluri, K;Snyder, SH

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聚(ADP-核糖)聚合酶-1(PARP-1; EC 2.4.2.30)是一种丰富的核酶,通过DNA链断裂激活以将多达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,我们研究了PARP-1靶向缺失的小鼠成纤维细胞中假型HIV I型的感染。病毒感染在PARP-1敲除的成纤维细胞中几乎完全消除。这种对感染的保护反映了病毒整合到宿主基因组中的预防。这些发现表明PARP抑制剂在治疗HIV I型感染中的潜力。
Poly(ADP-ribose) polymerase-1 (PARP-1; EC 2.4.2.30) 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.