title: TopoisomeraseIIβ in HIV-1 transactivation.
abstract: TopoisomeraseIIβ, an isoform of type II topoisomerase, was found to be functional in various viral infections. Its plausible role in HIV life cycle was also suggested earlier, but not clearly established. In the present study, we have investigated the role of TopoIIβ in HIV-1 infection by its gain and loss of function. Overexpression of TopoIIβ lead to an increase in viral replication, resulting in enhanced virion production. HIV-1 replication was impaired when TopoIIβ was down regulated by siRNA and inhibited by ICRF-193 and merbarone. The role of TopoIIβ in HIV-1 transcription was shown through its interaction with Tat and recruitement to long terminal repeat (LTR) region by co-immunoprecipitation and ChIP assays. Involvement of TopoIIβ in transactivation of HIV-1 LTR was confirmed by luciferase assay in reporter cell line, TZM bl and also by transfection of reporter exogenously. It was also observed that LTR transactivation commensurated with the expression of TopoIIβ in the presence of Tat. In addition, a decreased viral gene expression on treatment with merbarone exemplifies the importance of catalytic activity of TopoIIβ in viral replication. These observations indicate that TopoIIβ is involved in the cascade of coactivator complexes that are recruited to LTR for regulation of HIV-1 transcription.
authors.affiliation: Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad 500046, India.
authors.forename: Anil
authors.initials: A
authors.lastname: Chekuri
authors.affiliation: Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad 500046, India.
authors.forename: C
authors.initials: C
authors.lastname: Bhaskar
authors.affiliation: Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad 500046, India.
authors.forename: V Satish
authors.initials: VS
authors.lastname: Bollimpelli
authors.affiliation: Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad 500046, India. Electronic address: akondapi@gmail.com.
authors.forename: Anand K
authors.initials: AK
authors.lastname: Kondapi
mesh_terms: D034961:Antigens, Nuclear / Q000378:metabolism; D045744:Cell Line, Tumor; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D057809:HEK293 Cells; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D000072200:Ku Autoantigen; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D015533:Transcriptional Activation; D014779:Virus Replication; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000378:metabolism
chemical_list: D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen; D004250:DNA Topoisomerases, Type II
keywords: HIV-1 LTR; HIV-1 transcriptional regulation; KU70; PARP-1; Tat; TopoisomeraseIIβ