Lethal Mutagenesis of Hepatitis C Virus Induced by Favipiravir

被引：52

作者：

de Avilla, Ana I. ^{[1
]}

Gallego, Isabel ^{[1
,2
]}

Soria, Maria Eugenia ^{[3
]}

Gregori, Josep ^{[2
,3
,4
]}

Quer, Josep ^{[2
,3
,5
]}

Esteban, Juan Ignacio ^{[2
,3
,5
]}

Rice, Charles M. ^{[6
]}

Domingo, Esteban ^{[1
,2
]}

Perales, Celia ^{[1
,2
,3
]}

机构：

[1] UAM, CSIC, Ctr Biol Mol Severo Ochoa, Madrid 28049, Spain

[2] CIBERehd, Barcelona, Spain

[3] Univ Autonoma Barcelona, VHIR HUVH, Lab Malalties Hepat, Liver Unit,Internal Med, Barcelona 08035, Spain

[4] Roche Diagnost SL, Sant Cugat Del Valles, Spain

[5] Univ Autonoma Barcelona, Barcelona, Spain

[6] Rockefeller Univ, Ctr Study Hepatitis C, Lab Virol & Infect Dis, New York, NY 10021 USA

来源：

PLOS ONE | 2016年 / 11卷 / 10期

关键词：

HCV GENOTYPE 1; SOFOSBUVIR PLUS RIBAVIRIN; TREATMENT-NAIVE PATIENTS; MOUTH-DISEASE VIRUS; TREATMENT-EXPERIENCED PATIENTS; IN-VIVO ACTIVITIES; OPEN-LABEL; T-705; FAVIPIRAVIR; POLYMERASE INHIBITOR; PEGYLATED INTERFERON;

D O I：

10.1371/journal.pone.0164691

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

A 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 mutagen. Here we show that favipiravir (T-705) is a potent mutagenic agent for hepatitis C virus (HCV) during its replication in human hepatoma cells. T-705 leads to an excess of G -> A and C -> U transitions in the mutant spectrum of preextinction HCV populations. Infectivity decreased significantly in the presence of concentrations of T-705 which are 2- to 8-fold lower than its cytotoxic concentration 50 (CC50). Passaging the virus five times in the presence of 400 mu M T-705 resulted in virus extinction. Since T-705 has undergone advanced clinical trials for approval for human use, the results open a new approach based on lethal mutagenesis to treat hepatitis C virus infections. If proven effective for HCV in vivo, this new anti-HCV agent may be useful in patient groups that fail current therapeutic regimens.

引用

页数：19

共 105 条

[1] Ledipasvir and Sofosbuvir for Untreated HCV Genotype 1 Infection [J].

Afdhal, Nezam ;

Zeuzem, Stefan ;

Kwo, Paul ;

Chojkier, Mario ;

Gitlin, Norman ;

Puoti, Massimo ;

Romero-Gomez, Manuel ;

Zarski, Jean-Pierre ;

Agarwal, Kosh ;

Buggisch, Peter ;

Foster, Graham R. ;

Braeu, Norbert ;

Buti, Maria ;

Jacobson, Ira M. ;

Subramanian, G. Mani ;

Ding, Xiao ;

Mo, Hongmei ;

Yang, Jenny C. ;

Pang, Phillip S. ;

Symonds, William T. ;

McHutchison, John G. ;

Muir, Andrew J. ;

Mangia, Alessandra ;

Marcellin, Patrick .

NEW ENGLAND JOURNAL OF MEDICINE, 2014, 370 (20) :1889-1898

[2] Ledipasvir and Sofosbuvir for Previously Treated HCV Genotype 1 Infection [J].

Afdhal, Nezam ;

Reddy, K. Rajender ;

Nelson, David R. ;

Lawitz, Eric ;

Gordon, Stuart C. ;

Schiff, Eugene ;

Nahass, Ronald ;

Ghalib, Reem ;

Gitlin, Norman ;

Herring, Robert ;

Lalezari, Jacob ;

Younes, Ziad H. ;

Pockros, Paul J. ;

Di Bisceglie, Adrian M. ;

Arora, Sanjeev ;

Subramanian, G. Mani ;

Zhu, Yanni ;

Dvory-Sobol, Hadas ;

Yang, Jenny C. ;

Pang, Phillip S. ;

Symonds, William T. ;

McHutchison, John G. ;

Muir, Andrew J. ;

Sulkowski, Mark ;

Kwo, Paul .

NEW ENGLAND JOURNAL OF MEDICINE, 2014, 370 (16) :1483-1493

[3] Molecular characterization of a dual inhibitory and mutagenic activity of 5-fluorouridine triphosphate on viral RNA synthesis. Implications for lethal mutagenesis [J].

Agudo, Ruben ;

Arias, Armando ;

Pariente, Nonia ;

Perales, Celia ;

Escarmis, Cristina ;

Jorge, Alberto ;

Marina, Anabel ;

Domingo, Esteban .

JOURNAL OF MOLECULAR BIOLOGY, 2008, 382 (03) :652-666

[4] Involvement of a joker mutation in a polymerase-independent lethal mutagenesis escape mechanism [J].

Agudo, Ruben ;

de la Higuera, Ignacio ;

Arias, Armando ;

Grande-Perez, Ana ;

Domingo, Esteban .

VIROLOGY, 2016, 494 :257-266

[5] A Multi-Step Process of Viral Adaptation to a Mutagenic Nucleoside Analogue by Modulation of Transition Types Leads to Extinction-Escape [J].

Agudo, Ruben ;

Ferrer-Orta, Cristina ;

Arias, Armando ;

de la Higuera, Ignacio ;

Perales, Celia ;

Perez-Luque, Rosa ;

Verdaguer, Nuria ;

Domingo, Esteban .

PLOS PATHOGENS, 2010, 6 (08) :85-86

[6] Curing of foot-and-mouth disease virus from persistently infected cells by ribavirin involves enhanced mutagenesis [J].

Airaksinen, A ;

Pariente, N ;

Menéndez-Arias, L ;

Domingo, E .

VIROLOGY, 2003, 311 (02) :339-349

[7] Favipiravir elicits antiviral mutagenesis during virus replication in vivo [J].

Arias, Armando ;

Thorne, Lucy ;

Goodfellow, Ian .

ELIFE, 2014, 3 :e03679

[8] Direct-acting antivirals for the treatment of hepatitis C virus infection: optimizing current IFN-free treatment and future perspectives [J].

Asselah, Tarik ;

Boyer, Nathalie ;

Saadoun, David ;

Martinot-Peignoux, Michele ;

Marcellin, Patrick .

LIVER INTERNATIONAL, 2016, 36 :47-57

[9] Daclatasvir plus sofosbuvir for HCV infection: An oral combination therapy with high antiviral efficacy [J].

Asselah, Tarik .

JOURNAL OF HEPATOLOGY, 2014, 61 (02) :435-438

[10] T-705 (Favipiravir) Induces Lethal Mutagenesis in Influenza A H1N1 Viruses In Vitro [J].

Baranovich, Tatiana ;

Wong, Sook-San ;

Armstrong, Jianling ;

Marjuki, Henju ;

Webby, Richard J. ;

Webster, Robert G. ;

Govorkova, Elena A. .

JOURNAL OF VIROLOGY, 2013, 87 (07) :3741-3751

← 1 2 3 4 5 6 7 8 9 10 →