title: Poly(ADP-ribose) polymerase-1 silences retroviruses independently of viral DNA integration or heterochromatin formation.
abstract: PARP-1 silences retrotransposons in Drosophila, through heterochromatin maintenance, and integrated retroviruses in chicken. Here, we determined the role of viral DNA integration and cellular heterochromatin in PARP-1-mediated retroviral silencing using HIV-1-derived lentiviral vectors and Rous-associated virus type 1 (RAV-1) as models. Analysis of the infection of PARP-1 knockout and control cells with HIV-1 harbouring WT integrase, in the presence or absence of an integrase inhibitor, or catalytic-dead mutant integrase indicated that silencing does not require viral DNA integration. The mechanism involves the catalytic activity of histone deacetylases but not that of PARP-1. In contrast to Drosophila, lack of PARP-1 in avian cells did not affect chromatin compaction globally or at the RAV-1 provirus, or the cellular levels of histone H3 N-terminal acetylated or Lys27 trimethylated, as indicated by micrococcal nuclease accessibility and immunoblot assays. Therefore, PARP-1 represses retroviruses prior to viral DNA integration by mechanisms involving histone deacetylases but not heterochromatin formation.
authors.affiliation: Department of Biological Sciences, University of Texas at El Paso, 500 West University Ave., El Paso, TX 79968, USA.
authors.forename: Denisse A
authors.initials: DA
authors.lastname: Gutierrez
authors.affiliation: Department of Biological Sciences, University of Texas at El Paso, 500 West University Ave., El Paso, TX 79968, USA.
authors.forename: Luis
authors.initials: L
authors.lastname: Valdes
authors.affiliation: INSERM MIRCen LMB, Fontenay-aux-Roses, France.
authors.forename: Che
authors.initials: C
authors.lastname: Serguera
authors.affiliation: Department of Biological Sciences, University of Texas at El Paso, 500 West University Ave., El Paso, TX 79968, USA.
authors.forename: Manuel
authors.initials: M
authors.lastname: Llano
mesh_terms: D000818:Animals; D001354:Avian Leukosis Virus / Q000235:genetics* / Q000502:physiology; D002460:Cell Line; D002645:Chickens / Q000821:virology; D004279:DNA, Viral / Q000235:genetics*; D004330:Drosophila / Q000821:virology; D029721:Drosophila Proteins / Q000378:metabolism*; D019427:HIV Integrase / Q000235:genetics; D019428:HIV Integrase Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D006570:Heterochromatin / Q000235:genetics / Q000378:metabolism*; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000378:metabolism*; D000068898:Raltegravir Potassium / Q000494:pharmacology; D016662:Virus Integration / Q000235:genetics*
chemical_list: D004279:DNA, Viral; D029721:Drosophila Proteins; D019428:HIV Integrase Inhibitors; D006570:Heterochromatin; D006657:Histones; D000068898:Raltegravir Potassium; C524850:Parp protein, Drosophila; D000071137:Poly (ADP-Ribose) Polymerase-1; D019427:HIV Integrase; D006655:Histone Deacetylases