ADAR1 is a novel multi targeted anti-HIV-1 cellular protein

被引:34
作者
Biswas, Nabanita [1 ]
Wang, Tianyi [1 ]
Ding, Ming [1 ]
Tumne, Ashwin [1 ]
Chen, Yue [1 ]
Wang, Qingde [2 ]
Gupta, Phalguni [1 ]
机构
[1] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Infect Dis & Microbiol, Pittsburgh, PA 15261 USA
[2] Univ Pittsburgh, Inst Canc, Dept Med, Div Hematopoiesis & Oncol, Pittsburgh, PA 15213 USA
关键词
ADAR1; HW-1; Antiviral; Cellular protein; HUMAN-IMMUNODEFICIENCY-VIRUS; RNA ADENOSINE-DEAMINASE; VIRAL MESSENGER-RNA; REV TRANS-ACTIVATOR; HEPATITIS-C VIRUS; MEDIATED SUPPRESSION; BINDING DOMAIN; TYPE-1; AFFECTS; HUMAN-CELLS; HIV TYPE-1;
D O I
10.1016/j.virol.2011.10.024
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
We examined the antiviral activity of ADAR1 against HIV-1. Our results indicated that ADAR1 in a transfection system inhibited production of viral proteins and infectious HIV-1 in various cell lines including 293T, HeLa, Jurkat T and primary CD4+ T cells, and was active against a number of X4 and R5 HIV-1 of different clades. Further analysis showed that ADAR1 inhibited viral protein synthesis without any effect on viral RNA synthesis. Mutational analysis showed that ADAR1 introduced most of the A-to-G mutations in the rev RNA, in the region of RNA encoding for Rev Response Element (RRE) binding domain and in env RNA. These mutations inhibited the binding of rev to the RRE and inhibited transport of primary transcripts like gag, pol and env from nucleus to cytoplasm resulting in inhibition of viral protein synthesis without any effect on viral RNA synthesis. Furthermore, ADAR1 induced mutations in the env gene inhibited viral infectivity. (C) 2011 Elsevier Inc. All rights reserved.
引用
收藏
页码:265 / 277
页数:13
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