Hepatitis Monthly

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Prevalence of NS5B Resistance Mutations in Hepatitis C Virus (HCV) Treatment Naive South Africans

Maemu Petronella Gededzha 1 , * , M. Jeffrey Mphahlele 1 , 2 , Jason T. Blackard 3 and Selokela Gloria Selabe 1
Authors Information
1 HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University/National Health Laboratory Service, Pretoria, South Africa
2 South African Medical Research Council, Soutpansberg Road, Pretoria, South Africa
3 Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH, USA
Article information
  • Hepatitis Monthly: June 2017, 17 (6); e14248
  • Published Online: June 6, 2017
  • Article Type: Brief Report
  • Received: January 14, 2017
  • Revised: March 8, 2017
  • Accepted: May 13, 2017
  • DOI: 10.5812/hepatmon.14248

To Cite: Petronella Gededzha M, Mphahlele M J, Blackard J T, Gloria Selabe S. Prevalence of NS5B Resistance Mutations in Hepatitis C Virus (HCV) Treatment Naive South Africans, Hepat Mon. 2017 ; 17(6):e14248. doi: 10.5812/hepatmon.14248.

Copyright © 2017, Hepatitis Monthly. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.
1. Background
2. Methods
3. Results
4. Discussion
  • 1. Alter MJ. Epidemiology of hepatitis C virus infection. World J Gastroenterol. 2007; 13(17): 2436-41[PubMed]
  • 2. Lavanchy D. The global burden of hepatitis C. Liver Int. 2009; 29 Suppl 1: 74-81[DOI][PubMed]
  • 3. Smith DB, Bukh J, Kuiken C, Muerhoff AS, Rice CM, Stapleton JT, et al. Expanded classification of hepatitis C virus into 7 genotypes and 67 subtypes: updated criteria and genotype assignment web resource. Hepatology. 2014; 59(1): 318-27[DOI][PubMed]
  • 4. Paul D, Madan V, Bartenschlager R. Hepatitis C virus RNA replication and assembly: living on the fat of the land. Cell Host Microbe. 2014; 16(5): 569-79[DOI][PubMed]
  • 5. Ivashkina N, Wolk B, Lohmann V, Bartenschlager R, Blum HE, Penin F, et al. The hepatitis C virus RNA-dependent RNA polymerase membrane insertion sequence is a transmembrane segment. J Virol. 2002; 76(24): 13088-93[PubMed]
  • 6. Bressanelli S, Tomei L, Roussel A, Incitti I, Vitale RL, Mathieu M, et al. Crystal structure of the RNA-dependent RNA polymerase of hepatitis C virus. Proc Natl Acad Sci U S A. 1999; 96(23): 13034-9[PubMed]
  • 7. Kieffer TL, Kwong AD, Picchio GR. Viral resistance to specifically targeted antiviral therapies for hepatitis C (STAT-Cs). J Antimicrob Chemother. 2010; 65(2): 202-12[DOI][PubMed]
  • 8. Dubuisson J. Hepatitis C virus proteins. World J Gastroenterol. 2007; 13(17): 2406-15[PubMed]
  • 9. Ruhl M, Knuschke T, Schewior K, Glavinic L, Neumann-Haefelin C, Chang DI, et al. CD8+ T-cell response promotes evolution of hepatitis C virus nonstructural proteins. Gastroenterology. 2011; 140(7): 2064-73[DOI][PubMed]
  • 10. Neumann-Haefelin C, Oniangue-Ndza C, Kuntzen T, Schmidt J, Nitschke K, Sidney J, et al. Human leukocyte antigen B27 selects for rare escape mutations that significantly impair hepatitis C virus replication and require compensatory mutations. Hepatology. 2011; 54(4): 1157-66[DOI][PubMed]
  • 11. Romero-Lopez C, Berzal-Herranz A. A long-range RNA-RNA interaction between the 5' and 3' ends of the HCV genome. RNA. 2009; 15(9): 1740-52[DOI][PubMed]
  • 12. Romero-Lopez C, Berzal-Herranz A. The functional RNA domain 5BSL3.2 within the NS5B coding sequence influences hepatitis C virus IRES-mediated translation. Cell Mol Life Sci. 2012; 69(1): 103-13[DOI][PubMed]
  • 13. Tuplin A, Evans DJ, Simmonds P. Detailed mapping of RNA secondary structures in core and NS5B-encoding region sequences of hepatitis C virus by RNase cleavage and novel bioinformatic prediction methods. J Gen Virol. 2004; 85: 3037-47[DOI][PubMed]
  • 14. Tuplin A, Wood J, Evans DJ, Patel AH, Simmonds P. Thermodynamic and phylogenetic prediction of RNA secondary structures in the coding region of hepatitis C virus. RNA. 2002; 8(6): 824-41[PubMed]
  • 15. Friebe P, Boudet J, Simorre JP, Bartenschlager R. Kissing-loop interaction in the 3' end of the hepatitis C virus genome essential for RNA replication. J Virol. 2005; 79(1): 380-92[DOI][PubMed]
  • 16. Blackard JT, Ma G, Limketkai BN, Welge JA, Dryer PD, Martin CM, et al. Variability of the polymerase gene (NS5B) in hepatitis C virus-infected women. J Clin Microbiol. 2010; 48(11): 4256-9[DOI][PubMed]
  • 17. Ruhl M, Chhatwal P, Strathmann H, Kuntzen T, Bankwitz D, Skibbe K, et al. Escape from a dominant HLA-B*15-restricted CD8+ T cell response against hepatitis C virus requires compensatory mutations outside the epitope. J Virol. 2012; 86(2): 991-1000[DOI][PubMed]
  • 18. Guedj J, Rong L, Dahari H, Perelson AS. A perspective on modelling hepatitis C virus infection. J Viral Hepat. 2010; 17(12): 825-33[DOI][PubMed]
  • 19. Bacon BR, Khalid O. Triple therapy with boceprevir for HCV genotype 1 infection: phase III results in relapsers and nonresponders. Liver Int. 2012; 32 Suppl 1: 51-3[DOI][PubMed]
  • 20. Summary of recommendations for patients who are initiating therapy for HCV infection by HCV genotype. 2017;
  • 21. De Francesco R, Migliaccio G. Challenges and successes in developing new therapies for hepatitis C. Nature. 2005; 436(7053): 953-60[DOI][PubMed]
  • 22. Asahina Y, Izumi N, Enomoto N, Uchihara M, Kurosaki M, Onuki Y, et al. Mutagenic effects of ribavirin and response to interferon/ribavirin combination therapy in chronic hepatitis C. J Hepatol. 2005; 43(4): 623-9[DOI][PubMed]
  • 23. Keating GM, Vaidya A. Sofosbuvir: first global approval. Drugs. 2014; 74(2): 273-82[DOI][PubMed]
  • 24. FDA approves Viekira Pak to treat hepatitis C. 2017;
  • 25. Paolucci S, Fiorina L, Mariani B, Gulminetti R, Novati S, Barbarini G, et al. Naturally occurring resistance mutations to inhibitors of HCV NS5A region and NS5B polymerase in DAA treatment-naive patients. Virol J. 2013; 10: 355[DOI][PubMed]
  • 26. Lontok E, Harrington P, Howe A, Kieffer T, Lennerstrand J, Lenz O, et al. Hepatitis C virus drug resistance-associated substitutions: State of the art summary. Hepatology. 2015; 62(5): 1623-32[DOI][PubMed]
  • 27. Lok AS, Gardiner DF, Lawitz E, Martorell C, Everson GT, Ghalib R, et al. Preliminary study of two antiviral agents for hepatitis C genotype 1. N Engl J Med. 2012; 366(3): 216-24[DOI][PubMed]
  • 28. Gededzha MP, Selabe SG, Kyaw T, Rakgole JN, Blackard JT, Mphahlele MJ. Introduction of new subtypes and variants of hepatitis C virus genotype 4 in South Africa. J Med Virol. 2012; 84(4): 601-7[DOI][PubMed]
  • 29. van de Laar TJ, Molenkamp R, van den Berg C, Schinkel J, Beld MG, Prins M, et al. Frequent HCV reinfection and superinfection in a cohort of injecting drug users in Amsterdam. J Hepatol. 2009; 51(4): 667-74[DOI][PubMed]
  • 30. Murphy DG, Willems B, Deschenes M, Hilzenrat N, Mousseau R, Sabbah S. Use of sequence analysis of the NS5B region for routine genotyping of hepatitis C virus with reference to C/E1 and 5' untranslated region sequences. J Clin Microbiol. 2007; 45(4): 1102-12[DOI][PubMed]
  • 31. Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H, et al. Clustal W and Clustal X version 2.0. Bioinformatics. 2007; 23(21): 2947-8[DOI][PubMed]
  • 32. Drummond AJ, Suchard MA, Xie D, Rambaut A. Bayesian phylogenetics with BEAUti and the BEAST 1.7. Mol Biol Evol. 2012; 29(8): 1969-73[DOI][PubMed]
  • 33. Chen ZW, Li H, Ren H, Hu P. Global prevalence of pre-existing HCV variants resistant to direct-acting antiviral agents (DAAs): mining the GenBank HCV genome data. Sci Rep. 2016; 6: 20310[DOI][PubMed]
  • 34. Devogelaere B, Berke JM, Vijgen L, Dehertogh P, Fransen E, Cleiren E, et al. TMC647055, a potent nonnucleoside hepatitis C virus NS5B polymerase inhibitor with cross-genotypic coverage. Antimicrob Agents Chemother. 2012; 56(9): 4676-84[DOI][PubMed]
  • 35. Zeuzem S, Buggisch P, Agarwal K, Marcellin P, Sereni D, Klinker H, et al. The protease inhibitor, GS-9256, and non-nucleoside polymerase inhibitor tegobuvir alone, with ribavirin, or pegylated interferon plus ribavirin in hepatitis C. Hepatology. 2012; 55(3): 749-58[DOI][PubMed]
  • 36. Howe AY, Cheng H, Johann S, Mullen S, Chunduru SK, Young DC, et al. Molecular mechanism of hepatitis C virus replicon variants with reduced susceptibility to a benzofuran inhibitor, HCV-796. Antimicrob Agents Chemother. 2008; 52(9): 3327-38[DOI][PubMed]
  • 37. Lam AM, Espiritu C, Bansal S, Micolochick Steuer HM, Niu C, Zennou V, et al. Genotype and subtype profiling of PSI-7977 as a nucleotide inhibitor of hepatitis C virus. Antimicrob Agents Chemother. 2012; 56(6): 3359-68[DOI][PubMed]
  • 38. Franco S, Casadella M, Noguera-Julian M, Clotet B, Tural C, Paredes R, et al. No detection of the NS5B S282T mutation in treatment-naive genotype 1 HCV/HIV-1 coinfected patients using deep sequencing. J Clin Virol. 2013; 58(4): 726-9[DOI][PubMed]
  • 39. Prabdial-Sing N, Blackard JT, Puren AJ, Mahomed A, Abuelhassan W, Mahlangu J, et al. Naturally occurring resistance mutations within the core and NS5B regions in hepatitis C genotypes, particularly genotype 5a, in South Africa. Antiviral Res. 2016; 127: 90-8[DOI][PubMed]
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