Synergistic lethal mutagenesis of hepatitis C virus.


Journal

Antimicrobial agents and chemotherapy
ISSN: 1098-6596
Titre abrégé: Antimicrob Agents Chemother
Pays: United States
ID NLM: 0315061

Informations de publication

Date de publication:
09 09 2019
Historique:
medline: 2 10 2019
entrez: 2 10 2019
pubmed: 2 10 2019
Statut: ppublish

Résumé

Lethal mutagenesis is an antiviral approach that consists in extinguishing a virus by an excess of mutations acquired during replication in the presence of a mutagenic agent, often a nucleotide analogue. One of its advantages is its broad spectrum nature that renders the strategy potentially effective against emergent RNA viral infections. Here we describe synergistic lethal mutagenesis of hepatitis C virus (HCV) by a combination of favipiravir (T-705) and ribavirin. Synergy has been documented over a broad range of analogue concentrations using the Chou-Talalay method as implemented in the CompuSyn graphics, with average dose reduction index (DRI) above 1 (68.02±101.6 for favipiravir, and 5.83±6.07 for ribavirin), and average combination indices (CI) below 1 (0.52±0.28). Furthermore, analogue concentrations that individually did not extinguish high fitness HCV in ten serial infections, when used in combination they extinguished high fitness HCV in one to two passages. Although both analogues display a preference for G→A and C→U transitions, deep sequencing analysis of mutant spectra indicated a different preference of the two analogues for the mutation sites, thus unveiling a new possible synergy mechanism in lethal mutagenesis. Prospects of synergy among mutagenic nucleotides as a strategy to confront emerging viral infections are discussed.

Identifiants

pubmed: 31570400
pii: AAC.01653-19
doi: 10.1128/AAC.01653-19
pmc: PMC6879252
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2019 American Society for Microbiology.

Références

J Virol. 2014 Oct;88(20):12098-111
pubmed: 25122776
Antiviral Res. 2008 Dec;80(3):377-9
pubmed: 18762216
Antimicrob Agents Chemother. 2019 Jul 25;63(8):null
pubmed: 31085519
Antiviral Res. 2016 Feb;126:62-8
pubmed: 26711718
Antiviral Res. 2018 May;153:85-94
pubmed: 29524445
Antimicrob Agents Chemother. 2017 Oct 24;61(11):
pubmed: 28848019
Antimicrob Agents Chemother. 2010 Jan;54(1):126-33
pubmed: 19901093
PLoS One. 2018 Oct 3;13(10):e0204877
pubmed: 30281674
Antimicrob Agents Chemother. 2005 Mar;49(3):981-6
pubmed: 15728892
J Virol. 2009 Jun;83(11):5760-4
pubmed: 19321623
Virology. 2018 Oct;523:100-109
pubmed: 30107298
PLoS One. 2013 Dec 31;8(12):e83361
pubmed: 24391758
PLoS Negl Trop Dis. 2014 Apr 10;8(4):e2790
pubmed: 24722586
J Hepatol. 2018 Aug;69(2):461-511
pubmed: 29650333
J Virol. 2013 Jul;87(13):7593-607
pubmed: 23637397
Virology. 2003 Mar 30;308(1):37-47
pubmed: 12706088
Virus Res. 2005 Feb;107(2):165-71
pubmed: 15649562
Viruses. 2018 Feb 09;10(2):
pubmed: 29425176
J Hepatol. 2005 Oct;43(4):623-9
pubmed: 16098627
Clin Epigenetics. 2019 May 29;11(1):85
pubmed: 31142371
Future Med Chem. 2019 Jul;11(13):1645-1657
pubmed: 31469331
PLoS One. 2011 Jan 14;6(1):e15135
pubmed: 21264288
Antimicrob Agents Chemother. 2009 Jan;53(1):202-9
pubmed: 18955536
Antimicrob Agents Chemother. 2011 Feb;55(2):782-7
pubmed: 21115797
Evolution. 1990 Nov;44(7):1725-1737
pubmed: 28567811
Int J Mol Sci. 2015 Aug 19;16(8):19698-712
pubmed: 26295392
Trends Microbiol. 2013 Feb;21(2):56-62
pubmed: 23195922
J Virol. 2013 Jun;87(11):6172-81
pubmed: 23536652
Virology. 2016 Jun;493:227-37
pubmed: 27060566
Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1492-7
pubmed: 9990051
Virus Res. 2017 Jul 15;239:115-125
pubmed: 28040474
Virus Res. 2016 Sep 2;223:140-6
pubmed: 27449600
Proc Natl Acad Sci U S A. 2010 Jan 12;107(2):882-7
pubmed: 20080770
Antimicrob Agents Chemother. 2013 Nov;57(11):5202-8
pubmed: 23917318
J Virol. 2019 Jan 4;93(2):
pubmed: 30381482
Open Forum Infect Dis. 2019 Feb 22;6(3):ofz076
pubmed: 30949527
Expert Rev Mol Med. 2010 Jan 22;12:e4
pubmed: 20096141
PLoS Negl Trop Dis. 2018 Apr 19;12(4):e0006421
pubmed: 29672522
Antimicrob Agents Chemother. 2016 May 23;60(6):3786-93
pubmed: 27067341
Hepatology. 2008 Dec;48(6):1843-50
pubmed: 19003912
Bioinformatics. 2011 Nov 1;27(21):2957-63
pubmed: 21903629
Antimicrob Agents Chemother. 2007 Sep;51(9):3168-76
pubmed: 17606691
J Hepatol. 2016 Oct;65(4):727-733
pubmed: 27349488
J Virol. 2002 Dec;76(24):13001-14
pubmed: 12438626
Curr Top Microbiol Immunol. 2016;392:161-79
pubmed: 26210988
Gastroenterology. 2019 Jun;156(8):2313-2329.e7
pubmed: 30836093
Antiviral Res. 2014 Apr;104:84-92
pubmed: 24486952
Future Virol. 2013 Nov;8(11):1085-1094
pubmed: 24563658
J Infect Dis. 2016 Apr 15;213(8):1253-61
pubmed: 26655300
Antimicrob Agents Chemother. 2018 Aug 27;62(9):
pubmed: 29914957
Microb Drug Resist. 2019 Jul/Aug;25(6):944-950
pubmed: 30702389
Virus Res. 2017 Apr 2;233:105-112
pubmed: 28322918
Science. 2005 Jul 22;309(5734):623-6
pubmed: 15947137
PLoS Negl Trop Dis. 2013 Dec 26;7(12):e2614
pubmed: 24386500
J Math Biol. 2017 Jun;74(7):1589-1609
pubmed: 27714432
Microbiol Mol Biol Rev. 2012 Jun;76(2):159-216
pubmed: 22688811
Curr Opin Virol. 2014 Oct;8:10-5
pubmed: 24846716
Elife. 2014 Oct 21;3:e03679
pubmed: 25333492
J Virol. 2013 Apr;87(7):3741-51
pubmed: 23325689
Antiviral Res. 2013 May;98(2):273-83
pubmed: 23523552
Nat Med. 2000 Dec;6(12):1375-9
pubmed: 11100123
J Infect Dis. 2018 Jul 13;218(4):509-511
pubmed: 29762707
Rev Med Virol. 2006 Jan-Feb;16(1):37-48
pubmed: 16287208
Antivir Ther. 2017;22(5):447-451
pubmed: 28085003
Cancer Res. 2010 Jan 15;70(2):440-6
pubmed: 20068163
J Virol. 2009 Nov;83(22):11950-8
pubmed: 19726509
PLoS Genet. 2019 Jun 19;15(6):e1008181
pubmed: 31216276
Eur Biophys J. 2018 May;47(4):443-457
pubmed: 29397419
PLoS One. 2016 Oct 18;11(10):e0164691
pubmed: 27755573
Antiviral Res. 2010 May;86(2):121-7
pubmed: 19874853
Pharmacol Rev. 2006 Sep;58(3):621-81
pubmed: 16968952
Proc Jpn Acad Ser B Phys Biol Sci. 2017;93(7):449-463
pubmed: 28769016
Naturwissenschaften. 1977 Nov;64(11):541-65
pubmed: 593400
J Infect Dis. 2016 Mar 15;213(6):934-8
pubmed: 26531247
J Mol Biol. 2012 Jun 8;419(3-4):158-70
pubmed: 22426127
Curr Top Microbiol Immunol. 2016;392:61-120
pubmed: 26597856
PLoS Med. 2018 Mar 27;15(3):e1002535
pubmed: 29584730
Antimicrob Agents Chemother. 2013 Oct;57(10):4673-80
pubmed: 23856782
J Hepatol. 2016 Oct;65(4):719-726
pubmed: 27084592
Antimicrob Agents Chemother. 2002 Apr;46(4):977-81
pubmed: 11897578
PLoS One. 2013 Aug 16;8(8):e71039
pubmed: 23976977
Future Virol. 2008 Nov;3(6):553-566
pubmed: 19727424
PLoS Negl Trop Dis. 2011 Oct;5(10):e1342
pubmed: 22022624
PLoS One. 2013 Jul 10;8(7):e68347
pubmed: 23874596
J Virol. 2018 Sep 12;92(19):
pubmed: 30045981
J Virol. 2017 Apr 28;91(10):
pubmed: 28275194
Antiviral Res. 2005 Jul;67(1):1-9
pubmed: 15890415
J Antimicrob Chemother. 2009 Oct;64(4):741-6
pubmed: 19643775
PLoS One. 2008;3(11):e3725
pubmed: 19008960
Am J Cancer Res. 2015 Dec 15;6(1):97-104
pubmed: 27073727
Sci Rep. 2015 Oct 12;5:14775
pubmed: 26456301
Nat Biotechnol. 2010 Feb;28(2):167-71
pubmed: 20118917
Antiviral Res. 2009 Jun;82(3):95-102
pubmed: 19428599

Auteurs

Isabel Gallego (I)

Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Consejo Superior de Investigaciones Científicas (CSIC), Campus de Cantoblanco, 28049, Madrid, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, 28029, Madrid, Spain.

María Eugenia Soria (ME)

Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Consejo Superior de Investigaciones Científicas (CSIC), Campus de Cantoblanco, 28049, Madrid, Spain.

Josep Gregori (J)

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, 28029, Madrid, Spain.
Liver Unit, Internal Medicine Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca (VHIR), 08035, Barcelona, Spain.
Roche Diagnostics, S.L., Sant Cugat del Vallés, 08174, Barcelona, Spain.

Ana I de Ávila (AI)

Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Consejo Superior de Investigaciones Científicas (CSIC), Campus de Cantoblanco, 28049, Madrid, Spain.

Carlos García-Crespo (C)

Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Consejo Superior de Investigaciones Científicas (CSIC), Campus de Cantoblanco, 28049, Madrid, Spain.

Elena Moreno (E)

Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Consejo Superior de Investigaciones Científicas (CSIC), Campus de Cantoblanco, 28049, Madrid, Spain.

Ignacio Gadea (I)

Department of Clinical Microbiology, IIS-Fundación Jiménez Díaz, UAM. Av. Reyes Católicos 2, 28040 Madrid, Spain.

Jaime Esteban (J)

Department of Clinical Microbiology, IIS-Fundación Jiménez Díaz, UAM. Av. Reyes Católicos 2, 28040 Madrid, Spain.

Ricardo Fernández-Roblas (R)

Department of Clinical Microbiology, IIS-Fundación Jiménez Díaz, UAM. Av. Reyes Católicos 2, 28040 Madrid, Spain.

Juan Ignacio Esteban (JI)

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, 28029, Madrid, Spain.
Liver Unit, Internal Medicine Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca (VHIR), 08035, Barcelona, Spain.
Universitat Autónoma de Barcelona, 08193, Barcelona, Spain.

Jordi Gómez (J)

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, 28029, Madrid, Spain.
Instituto de Parasitología y Biomedicina 'López-Neyra' (CSIC), Parque Tecnológico Ciencias de la Salud, Armilla, 18016, Granada, Spain.

Josep Quer (J)

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, 28029, Madrid, Spain.
Liver Unit, Internal Medicine Hospital Universitari Vall d'Hebron, Vall d'Hebron Institut de Recerca (VHIR), 08035, Barcelona, Spain.
Universitat Autónoma de Barcelona, 08193, Barcelona, Spain.

Esteban Domingo (E)

Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Consejo Superior de Investigaciones Científicas (CSIC), Campus de Cantoblanco, 28049, Madrid, Spain edomingo@cbm.csic.es cperales@cbm.csic.es.
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, 28029, Madrid, Spain.

Celia Perales (C)

Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Consejo Superior de Investigaciones Científicas (CSIC), Campus de Cantoblanco, 28049, Madrid, Spain edomingo@cbm.csic.es cperales@cbm.csic.es.
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, 28029, Madrid, Spain.
Department of Clinical Microbiology, IIS-Fundación Jiménez Díaz, UAM. Av. Reyes Católicos 2, 28040 Madrid, Spain.

Classifications MeSH