DYRK1A Controls HIV-1 Replication at a Transcriptional Level in an NFAT Dependent Manner.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read Online Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science
    • Subject Terms:
      HIV Long Terminal Repeat/*physiology ; HIV-1/*physiology ; NFATC Transcription Factors/*metabolism ; Protein Serine-Threonine Kinases/*metabolism ; Protein-Tyrosine Kinases/*metabolism ; Transcription, Genetic/*physiology ; Virus Replication/*physiology; HEK293 Cells ; Humans ; NFATC Transcription Factors/genetics ; Protein Binding ; Protein Serine-Threonine Kinases/genetics ; Protein-Tyrosine Kinases/genetics ; Dyrk Kinases
    • Abstract:
      Background: Transcription of the HIV-1 provirus is regulated by both viral and host proteins and is very important in the context of viral latency. In latently infected cells, viral gene expression is inhibited as a result of the sequestration of host transcription factors and epigenetic modifications.
      Results: In our present study we analyzed the effect of host factor dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) on HIV-1 replication. We show that DYRK1A controls HIV-1 replication by regulating provirus transcription. Downregulation or inhibition of DYRK1A increased LTR-driven transcription and viral replication in cell lines and primary PBMC. Furthermore, inhibition of DYRK1A resulted in reactivation of latent HIV-1 provirus to a similar extent as two commonly used broad-spectrum HDAC inhibitors. We observed that DYRK1A regulates HIV-1 transcription via the Nuclear Factor of Activated T-cells (NFAT) by promoting its translocation from the nucleus to the cytoplasm. Therefore, inhibition of DYRK1A results in increased nuclear levels of NFAT and increased NFAT binding to the viral LTR and thus increasing viral transcription.
      Conclusions: Our data indicate that host factor DYRK1A plays a role in the regulation of viral transcription and latency. Therefore, DYRK1A might be an attractive candidate for therapeutic strategies targeting the viral reservoir.
    • References:
      PLoS Pathog. 2009 May;5(5):e1000437. (PMID: 19478882)
      Cell Host Microbe. 2008 Mar 13;3(3):158-67. (PMID: 18329615)
      J Virol. 2006 Jan;80(1):130-7. (PMID: 16352537)
      Nature. 2008 Jan 24;451(7177):425-30. (PMID: 18200009)
      Nature. 2006 Jun 1;441(7093):646-50. (PMID: 16511445)
      Nature. 2004 Feb 26;427(6977):848-53. (PMID: 14985764)
      J Immunol Methods. 2001 Jan 1;247(1-2):141-51. (PMID: 11150545)
      J Virol. 1998 Apr;72(4):2855-64. (PMID: 9525605)
      J Virol. 1995 Nov;69(11):6705-11. (PMID: 7474080)
      Clin Immunol. 2000 Mar;94(3):179-91. (PMID: 10692237)
      J Biol Chem. 2001 Oct 26;276(43):39819-24. (PMID: 11518709)
      Nat Methods. 2006 Sep;3(9):715-9. (PMID: 16929317)
      J Viral Hepat. 2016 Mar;23 (3):191-201. (PMID: 26456011)
      J Virol. 2009 Aug;83(16):8289-92. (PMID: 19474095)
      Nat Med. 2014 Apr;20(4):425-9. (PMID: 24658076)
      EMBO J. 2001 Apr 2;20(7):1726-38. (PMID: 11285236)
      Nature. 2011 Jun 29;474(7353):658-61. (PMID: 21720370)
      J Mol Biol. 2009 Oct 16;393(1):98-112. (PMID: 19683540)
      J Virol. 2004 Jun;78(11):6073-6. (PMID: 15141007)
      Nature. 2012 Jul 25;487(7408):482-5. (PMID: 22837004)
      J Biol Chem. 1990 Oct 5;265(28):17174-9. (PMID: 2211619)
      Nat Med. 2001 May;7(5):631-4. (PMID: 11329067)
      Nat Protoc. 2008;3(3):363-70. (PMID: 18323807)
      PLoS Biol. 2005 Feb;3(2):e41. (PMID: 15719057)
      Virology. 2005 Sep 1;339(2):281-8. (PMID: 15993456)
      AIDS. 1991 Jun;5(6):663-8. (PMID: 1883541)
      Cell Host Microbe. 2013 Oct 16;14(4):398-410. (PMID: 24055605)
      EMBO J. 1996 Mar 1;15(5):1112-20. (PMID: 8605881)
      Structure. 2008 May;16(5):684-94. (PMID: 18462673)
      Eur J Paediatr Neurol. 2008 May;12(3):168-82. (PMID: 17933568)
      J Clin Invest. 2013 Jun;123(6):2475-87. (PMID: 23635774)
      Dev Biol. 2002 Jun 15;246(2):259-73. (PMID: 12051815)
      Nature. 2013 Oct 24;502(7472):559-62. (PMID: 24048477)
      Blood. 2009 Jan 1;113(1):58-65. (PMID: 18849485)
      Cell. 1978 May;14(1):115-21. (PMID: 667928)
      J Biol Chem. 2002 Sep 20;277(38):35156-61. (PMID: 12138125)
      Immunity. 1997 Mar;6(3):235-44. (PMID: 9075924)
      EMBO J. 2004 Jun 16;23(12):2369-80. (PMID: 15152190)
      Mol Cell Biol. 1987 Jan;7(1):379-87. (PMID: 3031469)
      Cell. 1978 May;14(1):105-13. (PMID: 667927)
      J Biol Chem. 2010 Apr 23;285(17):13223-32. (PMID: 20167603)
      ScientificWorldJournal. 2006 Jun 17;6:1911-22. (PMID: 17205196)
      PLoS One. 2010 Feb 17;5(2):e9276. (PMID: 20174665)
      Nature. 1987 Apr 16-22;326(6114):711-3. (PMID: 3031512)
      Nature. 2013 Oct 24;502(7472):563-6. (PMID: 24121441)
      Retrovirology. 2009 Aug 27;6:78. (PMID: 19712452)
      Mol Cell Neurosci. 2007 Oct;36(2):270-9. (PMID: 17720532)
      Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8392-6. (PMID: 7690960)
      Virology. 1995 Feb 1;206(2):935-44. (PMID: 7531918)
      Biotechnol J. 2010 Jan;5(1):39-49. (PMID: 20013946)
      Cell. 2008 Oct 3;135(1):49-60. (PMID: 18854154)
      Science. 2008 Feb 15;319(5865):921-6. (PMID: 18187620)
      Mol Cell Biol. 2002 Sep;22(18):6636-47. (PMID: 12192061)
      Proc Natl Acad Sci U S A. 2014 May 13;111(19):7078-83. (PMID: 24706775)
      PLoS One. 2011 Feb 25;6(2):e17190. (PMID: 21364930)
      J Biol Chem. 1978 May 25;253(10):3364-6. (PMID: 649576)
      Nature. 2006 Jun 1;441(7093):595-600. (PMID: 16554754)
      Biochem J. 2001 May 1;355(Pt 3):597-607. (PMID: 11311120)
      Nature. 1989 May 4;339(6219):70-3. (PMID: 2654643)
      Nat Commun. 2010 Oct 05;1:86. (PMID: 20981014)
      Nature. 2011 May 25;474(7353):654-7. (PMID: 21613998)
      J Virol. 2000 Apr;74(8):3740-51. (PMID: 10729149)
      Cell Host Microbe. 2008 Nov 13;4(5):495-504. (PMID: 18976975)
      PLoS Pathog. 2014 Apr 10;10(4):e1004071. (PMID: 24722454)
      Nature. 2002 Aug 8;418(6898):646-50. (PMID: 12167863)
      Cereb Cortex. 2012 Dec;22(12):2867-77. (PMID: 22215728)
      AIDS Res Hum Retroviruses. 2009 Feb;25(2):207-12. (PMID: 19239360)
      J Virol. 2008 Dec;82(24):12585-8. (PMID: 18842727)
      EMBO J. 2003 Apr 15;22(8):1868-77. (PMID: 12682019)
      J Virol. 2000 Sep;74(18):8358-67. (PMID: 10954535)
      J Biol Chem. 2009 Jul 17;284(29):19463-73. (PMID: 19460752)
      Antimicrob Agents Chemother. 2002 Jun;46(6):1896-905. (PMID: 12019106)
      Retrovirology. 2013 Oct 24;10:119. (PMID: 24156240)
      Nature. 2004 Jul 29;430(6999):569-73. (PMID: 15243629)
    • Accession Number:
      0 (NFATC Transcription Factors)
      EC 2.7.10.1 (Protein-Tyrosine Kinases)
      EC 2.7.11.1 (Protein Serine-Threonine Kinases)
    • Publication Date:
      Date Created: 20151208 Date Completed: 20160617 Latest Revision: 20231213
    • Publication Date:
      20240829
    • Accession Number:
      PMC4979971
    • Accession Number:
      10.1371/journal.pone.0144229
    • Accession Number:
      26641855