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Journal of General Virology header logo Journal of General Virology

Volume 97, Issue 7

Poly(ADP-ribose) polymerase-1 silences retroviruses independently of viral DNA integration or heterochromatin formation No Access

Abstract

PARP-1 silences retrotransposons in , 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 , 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.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): heterochromatin , histone deacetylases , histone H3 post-translational modifications , PARP-1 , PARP-1 catalytic activity and retroviral silencing
© 2016 The Authors
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/content/journal/jgv/10.1099/jgv.0.000466
2016-07-01
2025-04-21
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References

  1. Ali S. S., Whitney J. C., Stevenson J., Robinson H., Howell P. L., Navarre W. W. 2013; Structural insights into the regulation of foreign genes in Salmonella by the Hha/H-NS complex. J Biol Chem 288:13356–13369 [View Article][PubMed]
     [Google Scholar]
  2. Altschul S. F., Madden T. L., Schäffer A. A., Zhang J., Zhang Z., Miller W., Lipman D. J., Schaffer A. A. 1997; Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25:3389–3402 [View Article][PubMed]
     [Google Scholar]
  3. Amé J. C., Spenlehauer C., de Murcia G. 2004; The PARP superfamily. Bioessays 26:882–893 [View Article][PubMed]
     [Google Scholar]
  4. Ariumi Y., Turelli P., Masutani M., Trono D. 2005; DNA damage sensors ATM, ATR, DNA-PKcs, and PARP-1 are dispensable for human immunodeficiency virus type 1 integration. J Virol 79:2973–2978 [View Article][PubMed]
     [Google Scholar]
  5. Baba T. W., Giroir B. P., Humphries E. H. 1985; Cell lines derived from avian lymphomas exhibit two distinct phenotypes. Virology (Auckl) 144:139–151 [View Article][PubMed]
     [Google Scholar]
  6. Baekelandt V., Claeys A., Cherepanov P., De Clercq E., De Strooper B., Nuttin B., Debyser Z. 2000; DNA-dependent protein kinase is not required for efficient lentivirus integration. J Virol 74:11278–11285 [View Article][PubMed]
     [Google Scholar]
  7. Barr S. D., Leipzig J., Shinn P., Ecker J. R., Bushman F. D. 2005; Integration targeting by avian sarcoma-leukosis virus and human immunodeficiency virus in the chicken genome. J Virol 79:12035–12044 [View Article][PubMed]
     [Google Scholar]
  8. Beitzel B., Bushman F. 2003; Construction and analysis of cells lacking the HMGA gene family. Nucleic Acids Res 31:5025–5032 [View Article][PubMed]
     [Google Scholar]
  9. Boehler C., Gauthier L. R., Mortusewicz O., Biard D. S., Saliou J. M., Bresson A., Sanglier-Cianferani S., Smith S., Schreiber V., Boussin F., Dantzer F. 2012; Poly(ADP-ribose) polymerase 3 (PARP3), a newcomer in cellular response to DNA damage and mitotic progression. Proc Natl Acad Sci U S A 108:2783–2788 [CrossRef]
     [Google Scholar]
  10. Bueno M. T., Reyes D., Valdes L., Saheba A., Urias E., Mendoza C., Fregoso O. I., Llano M. 2013; Poly(ADP-ribose) polymerase 1 promotes transcriptional repression of integrated retroviruses. J Virol 87:2496–2507 [View Article][PubMed]
     [Google Scholar]
  11. Bürkle A., Virág L. 2013; Poly(ADP-ribose): PARadigms and PARadoxes. Mol Aspects Med 34:1046–1065 [View Article][PubMed]
     [Google Scholar]
  12. Butler S. L., Hansen M. S., Bushman F. D. 2001; A quantitative assay for HIV DNA integration in vivo . Nat Med 7:631–634 [View Article][PubMed]
     [Google Scholar]
  13. Chou D. M., Adamson B., Dephoure N. E., Tan X., Nottke A. C., Hurov K. E., Gygi S. P., Colaiacovo M. P., Elledge S. J. 2010; A chromatin localization screen reveals poly (ADP ribose)-regulated recruitment of the repressive polycomb and NuRD complexes to sites of DNA damage. Proc Natl Acad Sci U S A 107:18475–18480 [View Article]
     [Google Scholar]
  14. Chung H. R., Dunkel I., Heise F., Linke C., Krobitsch S., Ehrenhofer-Murray A. E., Sperling S. R., Vingron M. 2010; The effect of micrococcal nuclease digestion on nucleosome positioning data. PLoS One 5:e15754 [View Article][PubMed]
     [Google Scholar]
  15. Cooper A., García M., Petrovas C., Yamamoto T., Koup R. A., Nabel G. J. 2013; HIV-1 causes CD4 cell death through DNA-dependent protein kinase during viral integration. Nat New Biol 498:376–379 [View Article][PubMed]
     [Google Scholar]
  16. Drogaris P., Villeneuve V., Pomiès C., Lee E. H., Bourdeau V., Bonneil E., Ferbeyre G., Verreault A., Thibault P. 2012; Histone deacetylase inhibitors globally enhance h3/h4 tail acetylation without affecting h3 lysine 56 acetylation. Sci Rep 2:220. [View Article][PubMed]
     [Google Scholar]
  17. Gaken J. A., Tavassoli M., Gan S. U., Vallian S., Giddings I., Darling D. C., Galea-Lauri J., Thomas M. G., Abedi H. et al. 1996; Efficient retroviral infection of mammalian cells is blocked by inhibition of poly(ADP-ribose) polymerase activity. J Virol 70:3992–4000[PubMed]
     [Google Scholar]
  18. Garcia-Rivera J. A., Bueno M. T., Morales E., Kugelman J. R., Rodriguez D. F., Llano M. 2010; Implication of serine residues 271, 273, and 275 in the human immunodeficiency virus type 1 cofactor activity of lens epithelium-derived growth factor/p75. J Virol 84:740–752 [View Article][PubMed]
     [Google Scholar]
  19. Gasiunas G., Sinkunas T., Siksnys V. 2014; Molecular mechanisms of CRISPR-mediated microbial immunity. Cell Mol Life Sci 71:449–465 [View Article]
     [Google Scholar]
  20. Ha H. C., Juluri K., Zhou Y., Leung S., Hermankova M., Snyder S. H. 2001; Poly(ADP-ribose) polymerase-1 is required for efficient HIV-1 integration. Proc Natl Acad Sci U S A 98:3364–3368 [View Article][PubMed]
     [Google Scholar]
  21. Hochegger H., Dejsuphong D., Fukushima T., Morrison C., Sonoda E., Schreiber V., Zhao G. Y., Saberi A., Masutani M. et al. 2006; Parp-1 protects homologous recombination from interference by Ku and ligase IV in vertebrate cells. EMBO J 25:1305–1314 [View Article][PubMed]
     [Google Scholar]
  22. Hoelzer K., Shackelton L. A., Parrish C. R. 2008; Presence and role of cytosine methylation in DNA viruses of animals. Nucleic Acids Res 36:2825–2837 [View Article][PubMed]
     [Google Scholar]
  23. Jenuwein T., Allis C. D. 2001; Translating the histone code. Science 293:1074–1080 [View Article]
     [Google Scholar]
  24. Ji Y., Tulin A. V. 2010; The roles of PARP1 in gene control and cell differentiation. Curr Opin Genetics Dev 20:512–518 [View Article][PubMed]
     [Google Scholar]
  25. Kameoka M., Nukuzuma S., Itaya A., Tanaka Y., Ota K., Ikuta K., Yoshihara K. 2004; RNA interference directed against poly(ADP-ribose) polymerase 1 efficiently suppresses human immunodeficiency virus type 1 replication in human cells. J Virol 78:8931–8934 [View Article][PubMed]
     [Google Scholar]
  26. Kameoka M., Nukuzuma S., Itaya A., Tanaka Y., Ota K., Inada Y., Ikuta K., Yoshihara K. 2005; Poly(ADP-ribose)polymerase-1 is required for integration of the human immunodeficiency virus type 1 genome near centromeric alphoid DNA in human and murine cells. Biochem Biophys Res Commun 334:412–417 [View Article][PubMed]
     [Google Scholar]
  27. Kantor B., Ma H., Webster-Cyriaque J., Monahan P. E., Kafri T. 2009; Epigenetic activation of unintegrated HIV-1 genomes by gut-associated short chain fatty acids and its implications for HIV infection. Proc Natl Acad Sci U S A 106:18786–18791 [View Article][PubMed]
     [Google Scholar]
  28. Kilzer J. M., Stracker T., Beitzel B., Meek K., Weitzman M., Bushman F. D. 2003; Roles of host cell factors in circularization of retroviral DNA. Virology (Auckl) 314:460–467 [View Article][PubMed]
     [Google Scholar]
  29. Kim J., Kim H. 2012; Recruitment and biological consequences of histone modification of H3K27me3 and H3K9me3. ILAR J 53:232–239 [View Article][PubMed]
     [Google Scholar]
  30. Kimura H. 2013; Histone modifications for human epigenome analysis. J Hum Genet 58:439–445 [View Article][PubMed]
     [Google Scholar]
  31. Ko H. L., Ng H. J., Goh E. H., Ren E. C. 2013; Reduced ADP-ribosylation by PARP1 natural polymorphism V762A and by PARP1 inhibitors enhance hepatitis B virus replication. J Viral Hepat 20:658–665 [View Article][PubMed]
     [Google Scholar]
  32. Kotova E., Jarnik M., Tulin A. V. 2010; Uncoupling of the transactivation and transrepression functions of PARP1 protein. Proc Natl Acad Sci U S A 107:6406–6411 [View Article][PubMed]
     [Google Scholar]
  33. Kotova E., Lodhi N., Jarnik M., Pinnola A. D., Ji Y., Tulin A. V. 2011; Drosophila histone H2A variant (H2Av) controls poly(ADP-ribose) polymerase 1 (PARP1) activation in chromatin. Proc Natl Acad Sci U S A 108:6205–6210 [View Article][PubMed]
     [Google Scholar]
  34. Koyama T., Sun B., Tokunaga K., Tatsumi M., Ishizaka Y. 2013; DNA damage enhances integration of HIV-1 into macrophages by overcoming integrase inhibition. Retrovirology 10:21 [View Article][PubMed]
     [Google Scholar]
  35. Krishnakumar R., Kraus W. L. 2010; The PARP side of the nucleus: Molecular actions, physiological outcomes, and clinical targets. Mol Cell 39:8–24 [View Article][PubMed]
     [Google Scholar]
  36. Larkin M. A., Blackshields G., Brown N. P., Chenna R., McGettigan P. A., McWilliam H., Valentin F., Wallace I. M., Wilm A., Lopez R., Thompson J. D., Gibson T. J., Higgins D. G. 2007; Clustal W and clustal X version 2.0. Bioinformatics 23:2947–2948 [View Article][PubMed]
     [Google Scholar]
  37. Lilley C. E., Carson C. T., Muotri A. R., Gage F. H., Weitzman M. D. 2005; DNA repair proteins affect the lifecycle of herpes simplex virus 1. Proc Natl Acad Sci U S A 102:5844–5849 [View Article][PubMed]
     [Google Scholar]
  38. Lilley C. E., Chaurushiya M. S., Boutell C., Everett R. D., Weitzman M. D. 2011; The intrinsic antiviral defense to incoming HSV-1 genomes includes specific DNA repair proteins and is counteracted by the viral protein ICP0. PLoS Pathog 7:e1002084 [View Article][PubMed]
     [Google Scholar]
  39. Ménissier de Murcia J., Ricoul M., Tartier L., Niedergang C., Huber A., Dantzer F., Schreiber V., Amé J. C., Dierich A. et al. 2003; Functional interaction between PARP-1 and PARP-2 in chromosome stability and embryonic development in mouse. EMBO J 22:2255–2263 [View Article][PubMed]
     [Google Scholar]
  40. Mitta B., Weber C. C., Rimann M., Fussenegger M. 2004; Design and in vivo characterization of self-inactivating human and non-human lentiviral expression vectors engineered for streptogramin-adjustable transgene expression. Nucleic Acids Res 32:e106 [View Article][PubMed]
     [Google Scholar]
  41. Mitta B., Weber C. C., Fussenegger M. 2005; In vivo transduction of HIV-1-derived lentiviral particles engineered for macrolide-adjustable transgene expression. J Gene Med 7:1400–1408 [View Article][PubMed]
     [Google Scholar]
  42. Morales V., Richard-Foy H. 2000; Role of histone N-terminal tails and their acetylation in nucleosome dynamics. Mol Cell Biol 20:7230–7237 [View Article][PubMed]
     [Google Scholar]
  43. Ohsaki E., Ueda K., Sakakibara S., Do E., Yada K., Yamanishi K. 2004; Poly(ADP-ribose) polymerase 1 binds to Kaposi's sarcoma-associated herpesvirus (KSHV) terminal repeat sequence and modulates KSHV replication in latency. J Virol 78:9936–9946 [View Article][PubMed]
     [Google Scholar]
  44. Orzalli M. H., Conwell S. E., Berrios C., DeCaprio J. A., Knipe D. M. 2013; Nuclear interferon-inducible protein 16 promotes silencing of herpesviral and transfected DNA. Proc Natl Acad Sci U S A 110:E4492E4501 [View Article][PubMed]
     [Google Scholar]
  45. Pinnola A., Naumova N., Shah M., Tulin A. V. 2007; Nucleosomal core histones mediate dynamic regulation of poly(ADP-ribose) polymerase 1 protein binding to chromatin and induction of its enzymatic activity. J Biol Chem 282:32511–32519 [View Article][PubMed]
     [Google Scholar]
  46. Pinsker W., Haring E., Hagemann S., Miller W. J. 2001; The evolutionary life history of P transposons: from horizontal invaders to domesticated neogenes. Chromosoma 110:148–158 [CrossRef]
     [Google Scholar]
  47. Randow F., Sale J. E. 2006; Retroviral transduction of DT40. Subcell Biochem 40:383–386[PubMed]
     [Google Scholar]
  48. Rass E., Grabarz A., Bertrand P., Lopez B. S. 2012; [Double strand break repair, one mechanism can hide another: alternative non-homologous end joining]. Cancer radiothérapie: journal de la Société française de radiothérapie oncologique 16:1–10 [View Article][PubMed]
     [Google Scholar]
  49. Ross P. J., Kennedy M. A., Parks R. J. 2009; Host cell detection of noncoding stuffer DNA contained in helper-dependent adenovirus vectors leads to epigenetic repression of transgene expression. J Virol 83:8409–8417 [View Article][PubMed]
     [Google Scholar]
  50. Sakurai Y., Komatsu K., Agematsu K., Matsuoka M. 2009; DNA double strand break repair enzymes function at multiple steps in retroviral infection. Retrovirology 6:114 [View Article][PubMed]
     [Google Scholar]
  51. Schneider W. M., Wu D. T., Amin V., Aiyer S., Roth M. J. 2012; Mulv IN mutants responsive to HDAC inhibitors enhance transcription from unintegrated retroviral DNA. Virology (Auckl) 426:188–196 [View Article][PubMed]
     [Google Scholar]
  52. Schreiner S., Kinkley S., Bürck C., Mund A., Wimmer P., Schubert T., Groitl P., Will H., Dobner T. 2013; SPOC1-mediated antiviral host cell response is antagonized early in human adenovirus type 5 infection. PLoS Pathog 9:e1003775 [View Article][PubMed]
     [Google Scholar]
  53. Siva A. C., Bushman F. 2002; Poly(ADP-ribose) polymerase 1 is not strictly required for infection of murine cells by retroviruses. J Virol 76:11904–11910 [View Article][PubMed]
     [Google Scholar]
  54. Sloan R. D., Wainberg M. A. 2011; The role of unintegrated DNA in HIV infection. Retrovirology 8:52 [View Article][PubMed]
     [Google Scholar]
  55. Tulin A., Stewart D., Spradling A. C. 2002; The Drosophila heterochromatic gene encoding poly(ADP-ribose) polymerase (PARP) is required to modulate chromatin structure during development. Genes & Development 16:2108–2119 [View Article][PubMed]
     [Google Scholar]
  56. Wang Z. Q., Auer B., Stingl L., Berghammer H., Haidacher D., Schweiger M., Wagner E. F. 1995; Mice lacking ADPRT and poly(ADP-ribosyl)ation develop normally but are susceptible to skin disease. Genes & Development 9:509–520 [View Article][PubMed]
     [Google Scholar]
  57. Weitzman M. D., Lilley C. E., Chaurushiya M. S. 2010; Genomes in conflict: maintaining genome integrity during virus infection. Annu Rev Microbiol 64:61–81 [View Article][PubMed]
     [Google Scholar]
  58. Yu S. S., Dan K., Chono H., Chatani E., Mineno J., Kato I. 2008; Transient gene expression mediated by integrase-defective retroviral vectors. Biochem Biophys Res Commun 368:942–947 [View Article][PubMed]
     [Google Scholar]
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Poly(ADP-ribose) polymerase-1 silences retroviruses independently of viral DNA integration or heterochromatin formation
J. Gen. Virol. 97, 1686 (2016); https://doi.org/10.1099/jgv.0.000466
/content/journal/jgv/10.1099/jgv.0.000466
/content/journal/jgv/10.1099/jgv.0.000466
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