title: ADAR1 is a novel multi targeted anti-HIV-1 cellular protein.
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.
authors: Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors: Nabanita
authors: N
authors: Biswas
authors: Tianyi
authors: T
authors: Wang
authors: Ming
authors: M
authors: Ding
authors: Ashwin
authors: A
authors: Tumne
authors: Yue
authors: Y
authors: Chen
authors: Qingde
authors: Q
authors: Wang
authors: Phalguni
authors: P
authors: Gupta
mesh_terms: D000243:Adenosine Deaminase / Q000494:pharmacology*; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000494:pharmacology*; D001483:Base Sequence; D002478:Cells, Cultured; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D015752:Genes, env / Q000187:drug effects / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D054298:Human Immunodeficiency Virus Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000187:drug effects; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D017434:Protein Structure, Tertiary; D012367:RNA, Viral / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D019380:Anti-HIV Agents; D054298:Human Immunodeficiency Virus Proteins; D012367:RNA, Viral; D016601:RNA-Binding Proteins; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase