Defective viral genomes from chikungunya virus are broad-spectrum antivirals and prevent virus dissemination in mosquitoes.

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: 101238921 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7374 (Electronic) Linking ISSN: 15537366 NLM ISO Abbreviation: PLoS Pathog Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science, c2005-
    • Subject Terms:
      Genome, Viral* ; Virus Replication*; Aedes/*virology ; Antiviral Agents/*pharmacology ; Chikungunya Fever/*transmission ; Chikungunya virus/*genetics ; Defective Viruses/*genetics; Animals ; Chikungunya Fever/immunology ; Chikungunya Fever/virology ; Chikungunya virus/growth & development ; Chikungunya virus/isolation & purification ; Humans ; Mosquito Vectors/virology
    • Abstract:
      Defective viral genomes (DVGs) are truncated and/or rearranged viral genomes produced during virus replication. Described in many RNA virus families, some of them have interfering activity on their parental virus and/or strong immunostimulatory potential, and are being considered in antiviral approaches. Chikungunya virus (CHIKV) is an alphavirus transmitted by Aedes spp. that infected millions of humans in the last 15 years. Here, we describe the DVGs arising during CHIKV infection in vitro in mammalian and mosquito cells, and in vivo in experimentally infected Aedes aegypti mosquitoes. We combined experimental and computational approaches to select DVG candidates most likely to have inhibitory activity and showed that, indeed, they strongly interfere with CHIKV replication both in mammalian and mosquito cells. We further demonstrated that some DVGs present broad-spectrum activity, inhibiting several CHIKV strains and other alphaviruses. Finally, we showed that pre-treating Aedes aegypti with DVGs prevented viral dissemination in vivo.
      Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: the methodology described in this work is the basis of U.S. Provisional Application No. 63/000,998
    • References:
      Virus Res. 2019 May;265:94-101. (PMID: 30894320)
      J Gen Virol. 1980 May;48(1):63-73. (PMID: 6155435)
      J Virol. 2015 Dec 16;90(5):2446-54. (PMID: 26676773)
      Emerg Microbes Infect. 2018 Sep 26;7(1):163. (PMID: 30254258)
      Am J Trop Med Hyg. 2007 Mar;76(3):405-7. (PMID: 17360859)
      J Virol. 2014 May;88(10):5217-27. (PMID: 24574404)
      J Gen Virol. 2014 Aug;95(Pt 8):1625-1633. (PMID: 24760760)
      Microbes Infect. 2017 Nov;19(11):496-504. (PMID: 28754345)
      PLoS One. 2011 Apr 29;6(4):e19447. (PMID: 21559384)
      PLoS Pathog. 2021 Sep 27;17(9):e1009277. (PMID: 34570820)
      J Infect Dis. 2009 Aug 15;200(4):516-23. (PMID: 19572805)
      Vaccine. 2013 Nov 19;31(48):5713-21. (PMID: 24099876)
      J Virol. 2013 Feb;87(3):1290-300. (PMID: 23175362)
      Nat Microbiol. 2017 May 22;2:17078. (PMID: 28530650)
      Braz J Infect Dis. 2017 Sep - Oct;21(5):540-544. (PMID: 28688628)
      PLoS Pathog. 2015 Sep 03;11(9):e1005122. (PMID: 26336095)
      Cell Host Microbe. 2018 Mar 14;23(3):353-365.e8. (PMID: 29503180)
      Virol J. 2017 Jul 24;14(1):138. (PMID: 28738877)
      Sci Rep. 2016 Jun 06;6:27459. (PMID: 27264908)
      PLoS Pathog. 2012 Sep;8(9):e1002897. (PMID: 23028310)
      Virol J. 2018 Aug 20;15(1):130. (PMID: 30126424)
      Viruses. 2014 Oct 23;6(10):3991-4004. (PMID: 25341663)
      Biosensors (Basel). 2019 Apr 17;9(2):. (PMID: 30999661)
      J Virol. 2013 Jul;87(14):7816-27. (PMID: 23678166)
      Vaccine. 2006 May 15;24(20):4290-6. (PMID: 16621180)
      Virology. 2018 Jun 20;521:138-148. (PMID: 29935423)
      J Virol. 2017 Sep 27;91(20):. (PMID: 28768856)
      Mol Ther. 2018 Oct 3;26(10):2507-2522. (PMID: 30078765)
      J Gen Virol. 2006 May;87(Pt 5):1259-1265. (PMID: 16603528)
      Nature. 2018 Jul;559(7715):490-497. (PMID: 30046071)
      Curr Opin Virol. 2018 Dec;33:74-80. (PMID: 30099321)
      J Gen Virol. 1981 Sep;56(Pt 1):175-84. (PMID: 6170730)
      PLoS Pathog. 2017 Oct 12;13(10):e1006650. (PMID: 29023600)
      Trends Microbiol. 2017 May;25(5):402-412. (PMID: 28262512)
      Pathog Glob Health. 2017 Sep;111(6):271-275. (PMID: 28829253)
      J Infect Dis. 2016 Dec 15;214(suppl 5):S482-S487. (PMID: 27920178)
      Viruses. 2019 Feb 20;11(2):. (PMID: 30791607)
      Vaccine. 2018 Jun 27;36(28):4039-4045. (PMID: 29861183)
      J Virol. 2008 Sep;82(17):8570-8. (PMID: 18579602)
      PLoS Pathog. 2013 Oct;9(10):e1003703. (PMID: 24204261)
      Annu Rev Virol. 2017 Sep 29;4(1):181-200. (PMID: 28961411)
      Adv Virus Res. 1954;2:59-79. (PMID: 13228257)
      Microorganisms. 2019 May 14;7(5):. (PMID: 31091828)
      Nature. 1977 Apr 28;266(5605):815-9. (PMID: 194158)
      Vaccine. 2011 Mar 24;29(15):2777-84. (PMID: 21320545)
      Sci Transl Med. 2015 Mar 18;7(279):279ra37. (PMID: 25787763)
      J Virol. 2011 Jan;85(2):1025-35. (PMID: 21047966)
      Cell Host Microbe. 2014 Jun 11;15(6):706-16. (PMID: 24922573)
      Microbes Infect. 2016 Dec;18(12):724-734. (PMID: 27989728)
      PLoS Negl Trop Dis. 2016 Jan 25;10(1):e0004402. (PMID: 26807575)
      Nat Microbiol. 2019 Jul;4(7):1075-1087. (PMID: 31160826)
      J Immunol. 2008 Apr 1;180(7):4910-8. (PMID: 18354215)
    • Accession Number:
      0 (Antiviral Agents)
    • Publication Date:
      Date Created: 20210208 Date Completed: 20210623 Latest Revision: 20240330
    • Publication Date:
      20240330
    • Accession Number:
      PMC7870000
    • Accession Number:
      10.1371/journal.ppat.1009110
    • Accession Number:
      33556143