Diversity in Proprotein Convertase Reactivity among Human Papillomavirus Types.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 101509722 Publication Model: Electronic Cited Medium: Internet ISSN: 1999-4915 (Electronic) Linking ISSN: 19994915 NLM ISO Abbreviation: Viruses Subsets: MEDLINE
    • Publication Information:
      Original Publication: Basel, Switzerland : MDPI
    • Subject Terms:
      Proprotein Convertases* ; Papillomavirus Infections*; Humans ; Furin ; Human Papillomavirus Viruses ; Human papillomavirus 16/genetics
    • Abstract:
      The cleavage of viral surface proteins by furin is associated with some viruses' high virulence and infectivity. The human papillomavirus (HPV) requires the proteolytic processing of its capsid proteins for activation before entry. Variability in reactivity with furin and other proprotein convertases (PCs) among HPV types was investigated. HPV16, the most prevalent and carcinogenic HPV type, reacted with PCs with the broadest selectivity compared to other types in reactions of pseudoviral particles with the recombinant PCs, furin, PC4, PC5, PACE4, and PC7. Proteolytic preactivation was assessed using a well-established entry assay into PC-inhibited cells based on the green fluorescent protein as a reporter. The inhibition of the target cell PC activity with serpin-based PC-selective inhibitors also showed a diversity of PC selectivity among HPV types. HPV16 reacted with furin at the highest rate compared to the other types in time-dependent preactivation reactions and produced the highest entry values standardized to pseudoviral particle concentration. The predominant expression of furin in keratinocytes and the high reactivity of HPV16 with this enzyme highlight the importance of selectively targeting furin as a potential antiviral therapeutic approach.
    • References:
      J Virol. 2018 May 14;92(11):. (PMID: 29593032)
      Rev Med Virol. 2015 Mar;25 Suppl 1:2-23. (PMID: 25752814)
      Mol Med. 2018 May 16;24(1):23. (PMID: 30134802)
      J Dent Res. 2015 Nov;94(11):1532-43. (PMID: 26353884)
      J Virol. 2005 Mar;79(5):2839-46. (PMID: 15709003)
      J Virol. 2008 Dec;82(24):12565-8. (PMID: 18829767)
      J Biol Chem. 1993 Nov 25;268(33):24887-91. (PMID: 8227051)
      J Biol Chem. 2013 Jul 26;288(30):21802-14. (PMID: 23744066)
      J Infect Dis. 2010 Dec 15;202(12):1789-99. (PMID: 21067372)
      Viruses. 2014 Dec 05;6(12):4856-79. (PMID: 25490765)
      Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1522-7. (PMID: 16432208)
      Proc Natl Acad Sci U S A. 2004 Jul 20;101(29):10560-5. (PMID: 15247425)
      Virology. 2013 Oct;445(1-2):224-31. (PMID: 23928291)
      J Virol. 2004 Jan;78(2):751-7. (PMID: 14694107)
      PLoS One. 2014 Jun 11;9(6):e99114. (PMID: 24918765)
      Thromb Haemost. 2006 Feb;95(2):243-52. (PMID: 16493485)
      Viruses. 2015 Jul 16;7(7):3863-90. (PMID: 26193301)
      Biochim Biophys Acta. 1995 Mar 15;1247(2):179-84. (PMID: 7696306)
      Mol Cell. 2000 Mar;5(3):557-67. (PMID: 10882140)
      Biochemistry. 2019 Mar 26;58(12):1679-1688. (PMID: 30848586)
      J Virol. 2016 Jun 24;90(14):6224-6234. (PMID: 27122588)
      Sci Rep. 2021 Feb 10;11(1):3498. (PMID: 33568731)
      Int J Clin Oncol. 2023 Aug;28(8):965-974. (PMID: 37294390)
      Nat Rev Drug Discov. 2012 May;11(5):367-83. (PMID: 22679642)
      PLoS One. 2013 Jul 04;8(7):e68379. (PMID: 23861898)
      Tumour Virus Res. 2023 Jun;15:200258. (PMID: 36812987)
      Curr Protoc Cell Biol. 2007 Dec;Chapter 26:Unit 26.1. (PMID: 18228512)
      Int J Cancer. 2012 Nov 15;131(10):2349-59. (PMID: 22323075)
      Biochem J. 2006 May 1;395(3):449-56. (PMID: 16445382)
      J Virol. 2018 Sep 26;92(20):. (PMID: 30045992)
      Biochemistry. 1974 Dec 17;13(26):5439-45. (PMID: 4547976)
      Viruses. 2015 Nov 11;7(11):5813-30. (PMID: 26569287)
      Vaccine. 2008 Aug 19;26 Suppl 10:K1-16. (PMID: 18847553)
      Pathogens. 2020 Mar 18;9(3):. (PMID: 32197385)
      Viruses. 2019 Sep 09;11(9):. (PMID: 31505793)
      Ecancermedicalscience. 2015 Apr 29;9:526. (PMID: 25987895)
      Br J Cancer. 2006 Jan 16;94(1):171-5. (PMID: 16404371)
      J Virol. 2008 Jun;82(11):5190-7. (PMID: 18367526)
    • Grant Information:
      R21 AI151674 United States AI NIAID NIH HHS
    • Contributed Indexing:
      Keywords: antivirals; furin; host proteases; human papillomavirus; proprotein convertases; protease inhibitors; virus activation; virus infectivity
    • Accession Number:
      EC 3.4.21.- (Proprotein Convertases)
      EC 3.4.21.75 (Furin)
    • Publication Date:
      Date Created: 20240123 Date Completed: 20240124 Latest Revision: 20241023
    • Publication Date:
      20241023
    • Accession Number:
      PMC10820984
    • Accession Number:
      10.3390/v16010039
    • Accession Number:
      38257739