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

• Published in: Virology (New York, N.Y.) N.Y.), 2012-01, Vol.422 (2), p.265-277
• Main Authors: Biswas, Nabanita, Wang, Tianyi, Ding, Ming, Tumne, Ashwin, Chen, Yue, Wang, Qingde, Gupta, Phalguni
• Format: Article
• Language: English
• Subjects: ADAR1; Adenosine Deaminase - pharmacology; Amino Acid Motifs; Amino Acid Sequence; Anti-HIV Agents - pharmacology; Antiviral; Base Sequence; Cells, Cultured; Cellular protein; Gene Expression Regulation, Viral - drug effects; Genes, env - drug effects; Genes, env - genetics; HIV-1; HIV-1 - drug effects; HIV-1 - genetics; HIV-1 - physiology; Human immunodeficiency virus 1; Human Immunodeficiency Virus Proteins - antagonists & inhibitors; Human Immunodeficiency Virus Proteins - biosynthesis; Human Immunodeficiency Virus Proteins - drug effects; Humans; Infectious Disease; Molecular Sequence Data; Mutation; Protein Structure, Tertiary; RNA, Viral - biosynthesis; RNA, Viral - drug effects; RNA, Viral - genetics; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2011.10.024

Abstract 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.