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Quasispecies and Drug Resistance

  • Celia PeralesEmail author
  • Ana M. Ortega-Prieto
  • Nathan M. Beach
  • Julie Sheldon
  • Luis Menéndez-Arias
  • Esteban Domingo
Reference work entry

Abstract

Mutant spectra of viral quasispecies are complex reservoirs of genetic and phenotypic variants, including drug-resistant mutants. Here we review basic features of RNA viral quasispecies such as internal interactions within mutant spectra and the effect of population size and bottleneck events as they affect the frequency of inhibitor-escape mutants. Genetic barriers to resistance and fitness cost of specific amino acid substitutions involved in resistance are discussed, with specific examples for human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV). Prospects for new antiviral designs aimed at counteracting the adaptive potential of viral quasispecies are presented.

Keywords

Antiviral therapy Drug resistance Genetic barrier Hepatitis C virus (HCV) Human immunodeficiency virus type 1 (HIV-1) Mutant spectrum Replication rate Viral fitness Viral load Viral quasispecies 

Notes

Acknowledgments

Work at Centro de Biología Molecular Severo Ochoa (CSIC-UAM) supported by grant BFU2011-23604 and Fundación Ramón Areces. N.M.B. is supported by a JAE-DOC contract from Consejo Superior de Investigaciones Científicas (CSIC) and J.S. by a Juan de la Cierva contract from CSIC. CIBERehd is funded by Instituto de Salud Carlos III. Work in the lab of Dr. Menéndez-Arias was supported in part by grants of the Spanish Ministries of Economy and Competitiveness (BIO2010/15542 and BIO2013-48788-C2-1-R) and Health, Social Services and Equality (EC11-025).

References

  1. Afdhal N, Reddy KR, Nelson DR et al (2014a) Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med 370:1483–1493PubMedCrossRefGoogle Scholar
  2. Afdhal N, Zeuzem S, Kwo P et al (2014b) Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med 370(20):1889–1898. doi:10.1056/NEJMoa1402454PubMedCrossRefGoogle Scholar
  3. Asahchop EL, Wainberg MA, Oliveira M et al (2013) Distinct resistance patterns to etravirine and rilpivirine in viruses containing nonnucleoside reverse transcriptase inhibitor mutations at baseline. Aids 27:879–887PubMedCrossRefGoogle Scholar
  4. Asahina Y, Izumi N, Enomoto N et al (2005) Mutagenic effects of ribavirin and response to interferon/ribavirin combination therapy in chronic hepatitis C. J Hepatol 43:623–629PubMedCrossRefGoogle Scholar
  5. Azijn H, Tirry I, Vingerhoets J et al (2010) TMC278, a next-generation nonnucleoside reverse transcriptase inhibitor (NNRTI), active against wild-type and NNRTI-resistant HIV-1. Antimicrob Agents Chemother 54:718–727PubMedCrossRefGoogle Scholar
  6. Bacon BR, Gordon SC, Lawitz E et al (2011) Boceprevir for previously treated chronic HCV genotype 1 infection. N Engl J Med 364:1207–1217PubMedPubMedCentralCrossRefGoogle Scholar
  7. Cao L, Wu C, Shi H et al (2014) Coexistence of hepatitis B virus quasispecies enhances viral replication and the ability to induce host antibody and cellular immune responses. J Virol 88:8656–8666PubMedPubMedCentralCrossRefGoogle Scholar
  8. Centers for Disease Control (1981) Pneumocystis pneumonia–Los Angeles. MMWR Morb Mortal Wkly Rep 30:250–252Google Scholar
  9. Chang MW, Torbett BE (2011) Accessory mutations maintain stability in drug-resistant HIV-1 protease. J Mol Biol 410:756–760PubMedPubMedCentralCrossRefGoogle Scholar
  10. Chatterji U, Lim P, Bobardt MD et al (2010) HCV resistance to cyclosporin A does not correlate with a resistance of the NS5A-cyclophilin A interaction to cyclophilin inhibitors. J Hepatol 53:50–56PubMedPubMedCentralCrossRefGoogle Scholar
  11. Chayama K, Hayes CN (2011) Hepatitis C virus: how genetic variability affects pathobiology of disease. J Gastroenterol Hepatol 26(Suppl 1):83–95PubMedCrossRefGoogle Scholar
  12. Chumakov KM, Powers LB, Noonan KE et al (1991) Correlation between amount of virus with altered nucleotide sequence and the monkey test for acceptability of oral poliovirus vaccine. Proc Natl Acad Sci U S A 88:199–203PubMedPubMedCentralCrossRefGoogle Scholar
  13. Clotet B, Menéndez-Arias L, Schapiro JM et al (2014) The HIV & hepatitis drug resistance and PK guide, 13th edn. Fundació de Lluita contra la SIDA, Barcelona, 706 ppGoogle Scholar
  14. Crowder S, Kirkegaard K (2005) Trans-dominant inhibition of RNA viral replication can slow growth of drug-resistant viruses. Nat Genet 37:701–709PubMedCrossRefGoogle Scholar
  15. Cuevas JM, Gonzalez-Candelas F, Moya A et al (2009) Effect of ribavirin on the mutation rate and spectrum of hepatitis C virus in vivo. J Virol 83:5760–5764PubMedPubMedCentralCrossRefGoogle Scholar
  16. de la Torre JC, Holland JJ (1990) RNA virus quasispecies populations can suppress vastly superior mutant progeny. J Virol 64:6278–6281PubMedPubMedCentralGoogle Scholar
  17. Delang L, Vliegen I, Froeyen M et al (2011) Comparative study of the genetic barriers and pathways towards resistance of selective inhibitors of hepatitis C virus replication. Antimicrob Agents Chemother 55:4103–4113PubMedPubMedCentralCrossRefGoogle Scholar
  18. deLemos AS, Chung RT (2014) Hepatitis C treatment: an incipient therapeutic revolution. Trends Mol Med 20:315–321PubMedCrossRefGoogle Scholar
  19. Dietz J, Schelhorn SE, Fitting D et al (2013) Deep sequencing reveals mutagenic effects of ribavirin during monotherapy of hepatitis C virus genotype 1-infected patients. J Virol 87:6172–6181PubMedPubMedCentralCrossRefGoogle Scholar
  20. Dixit NM, Layden-Almer JE, Layden TJ et al (2004) Modelling how ribavirin improves interferon response rates in hepatitis C virus infection. Nature 432:922–924PubMedCrossRefGoogle Scholar
  21. Domingo E (1989) RNA virus evolution and the control of viral disease. Prog Drug Res 33:93–133PubMedCrossRefGoogle Scholar
  22. Domingo E, Sabo D, Taniguchi T et al (1978) Nucleotide sequence heterogeneity of an RNA phage population. Cell 13:735–744PubMedCrossRefGoogle Scholar
  23. Domingo E, Sheldon J, Perales C (2012) Viral quasispecies evolution. Microbiol Mol Biol Rev 76:159–216PubMedPubMedCentralCrossRefGoogle Scholar
  24. Donaldson EF, Harrington PR, O’Rear JJ et al (2014) Clinical evidence and bioinformatics characterization of potential hepatitis C virus resistance pathways for sofosbuvir. Hepatology (in press)Google Scholar
  25. Duarte EA, Novella IS, Ledesma S et al (1994) Subclonal components of consensus fitness in an RNA virus clone. J Virol 68:4295–4301PubMedPubMedCentralGoogle Scholar
  26. Eggers HJ, Tamm I (1965) Coxsackie A9 virus: mutation from drug dependence to drug independence. Science 148:97–98PubMedCrossRefGoogle Scholar
  27. Eigen M (2013) From strange simplicity to complex familiarity. Oxford University Press, OxfordCrossRefGoogle Scholar
  28. Eigen M, Biebricher CK (1988) Sequence space and quasispecies distribution. In: Domingo E, Ahlquist P, Holland JJ (eds) RNA genetics. CRC Press, Boca Raton, pp 211–245Google Scholar
  29. Eigen M, Schuster P (1979) The hypercycle. A principle of natural self-organization. Springer, BerlinGoogle Scholar
  30. Enomoto N, Sakuma I, Asahina Y et al (1996) Mutations in the nonstructural protein 5A gene and response to interferon in patients with chronic hepatitis C virus 1b infection. N Engl J Med 334:77–81PubMedCrossRefGoogle Scholar
  31. Feigelstock DA, Mihalik KB, Feinstone SM (2011) Selection of hepatitis C virus resistant to ribavirin. Virol J 8:402PubMedPubMedCentralCrossRefGoogle Scholar
  32. Forns X, Lawitz E, Zeuzem S et al (2014) Simeprevir with peginterferon and ribavirin leads to high rates of SVR in patients with HCV genotype 1 who relapsed after previous therapy: a phase 3 trial. Gastroenterology. doi:10.1053/j.gastro.2014.02.051Google Scholar
  33. Fridell RA, Wang C, Sun JH et al (2011) Genotypic and phenotypic analysis of variants resistant to hepatitis C virus nonstructural protein 5A replication complex inhibitor BMS-790052 in humans: in vitro and in vivo correlations. Hepatology 54:1924–1935PubMedCrossRefGoogle Scholar
  34. Gao M (2013) Antiviral activity and resistance of HCV NS5A replication complex inhibitors. Curr Opin Virol 3:514–520PubMedCrossRefGoogle Scholar
  35. Ge D, Fellay J, Thompson AJ et al (2009) Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 461:399–401PubMedCrossRefGoogle Scholar
  36. Geller R, Vignuzzi M, Andino R et al (2007) Evolutionary constraints on chaperone-mediated folding provide an antiviral approach refractory to development of drug resistance. Genes Dev 21:195–205PubMedPubMedCentralCrossRefGoogle Scholar
  37. González-López C, Arias A, Pariente N et al (2004) Preextinction viral RNA can interfere with infectivity. J Virol 78:3319–3324PubMedPubMedCentralCrossRefGoogle Scholar
  38. Grande-Pérez A, Lázaro E, Lowenstein P et al (2005) Suppression of viral infectivity through lethal defection. Proc Natl Acad Sci U S A 102:4448–4452PubMedPubMedCentralCrossRefGoogle Scholar
  39. Greenberg ML, Cammack N (2004) Resistance to enfuvirtide, the first HIV fusion inhibitor. J Antimicrob Chemother 54:333–340PubMedCrossRefGoogle Scholar
  40. Gulick RM, Mellors JW, Havlir D et al (1997) Treatment with indinavir, zidovudine, and lamivudine in adults with human immunodeficiency virus infection and prior antiretroviral therapy. N Engl J Med 337:734–739PubMedCrossRefGoogle Scholar
  41. Halfon P, Sarrazin C (2012) Future treatment of chronic hepatitis C with direct acting antivirals: is resistance important? Liver Int 32(Suppl 1):79–87PubMedCrossRefGoogle Scholar
  42. Hammer SM, Squires KE, Hughes MD et al (1997) A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. AIDS Clinical Trials Group 320 Study Team. N Engl J Med 337:725–733PubMedCrossRefGoogle Scholar
  43. Hmwe SS, Aizaki H, Date T et al (2010) Identification of hepatitis C virus genotype 2a replicon variants with reduced susceptibility to ribavirin. Antiviral Res 85:520–524PubMedCrossRefGoogle Scholar
  44. Holland JJ (2006) Transitions in understanding of RNA viruses: an historical perspective. Curr Top Microbiol Immunol 299:371–401PubMedGoogle Scholar
  45. Hopkins S, Scorneaux B, Huang Z et al (2010) SCY-635, a novel nonimmunosuppressive analog of cyclosporine that exhibits potent inhibition of hepatitis C virus RNA replication in vitro. Antimicrob Agents Chemother 54:660–672PubMedCrossRefGoogle Scholar
  46. Horner SM, Gale M Jr (2013) Regulation of hepatic innate immunity by hepatitis C virus. Nat Med 19:879–888PubMedPubMedCentralCrossRefGoogle Scholar
  47. Ibarra KD, Pfeiffer JK (2009) Reduced ribavirin antiviral efficacy via nucleoside transporter-mediated drug resistance. J Virol 83:4538–4547PubMedPubMedCentralCrossRefGoogle Scholar
  48. Iranzo J, Perales C, Domingo E et al (2011) Tempo and mode of inhibitor-mutagen antiviral therapies: a multidisciplinary approach. Proc Natl Acad Sci U S A 108:16008–16013PubMedPubMedCentralCrossRefGoogle Scholar
  49. Jacobson IM, McHutchison JG, Dusheiko G et al (2011) Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med 364:2405–2416PubMedCrossRefGoogle Scholar
  50. Javanbakht H, Ptak RG, Chow E et al (2010) In vitro resistance development for RO-0335, a novel diphenylether nonnucleoside reverse transcriptase inhibitor. Antiviral Res 86:212–219PubMedCrossRefGoogle Scholar
  51. Kozuka R, Enomoto M, Hai H et al (2012) Changes in sequences of core region, interferon sensitivity-determining region and interferon and ribavirin resistance-determining region of hepatitis C virus genotype 1 during interferon-alpha and ribavirin therapy, and efficacy of retreatment. Hepatol Res 42:1157–1167PubMedCrossRefGoogle Scholar
  52. Kumar N, Liang Y, Parslow TG et al (2011) Receptor tyrosine kinase inhibitors block multiple steps of influenza a virus replication. J Virol 85:2818–2827PubMedPubMedCentralCrossRefGoogle Scholar
  53. Lange CM, Zeuzem S (2013) Perspectives and challenges of interferon-free therapy for chronic hepatitis C. J Hepatol 58:583–592PubMedCrossRefGoogle Scholar
  54. Lange CM, Sarrazin C, Zeuzem S (2010) Review article: specifically targeted anti-viral therapy for hepatitis C – a new era in therapy. Aliment Pharmacol Ther 32:14–28PubMedCrossRefGoogle Scholar
  55. Larder BA, Darby G, Richman DD (1989) HIV with reduced sensitivity to zidovudine (AZT) isolated during prolonged therapy. Science 243:1731–1734PubMedCrossRefGoogle Scholar
  56. Lenz O, de Bruijne J, Vijgen L et al (2012) Efficacy of re-treatment with TMC435 as combination therapy in hepatitis C virus-infected patients following TMC435 monotherapy. Gastroenterology 143(1176–1178):e1171–e1176Google Scholar
  57. Li MJ, Kim J, Li S et al (2005) Long-term inhibition of HIV-1 infection in primary hematopoietic cells by lentiviral vector delivery of a triple combination of anti-HIV shRNA, anti-CCR5 ribozyme, and a nucleolar-localizing TAR decoy. Mol Ther 12:900–909PubMedCrossRefGoogle Scholar
  58. Lutchman G, Danehower S, Song BC et al (2007) Mutation rate of the hepatitis C virus NS5B in patients undergoing treatment with ribavirin monotherapy. Gastroenterology 132:1757–1766PubMedCrossRefGoogle Scholar
  59. Mas A, Lopez-Galíndez C, Cacho I et al (2010) Unfinished stories on viral quasispecies and Darwinian views of evolution. J Mol Biol 397:865–877PubMedCrossRefGoogle Scholar
  60. Mauss S, Berg T, Rockstroh J et al (2014) Short guide to hepatitis C. Flying Publisher & Kamps, GermanyGoogle Scholar
  61. McCown MF, Rajyaguru S, Le Pogam S et al (2008) The hepatitis C virus replicon presents a higher barrier to resistance to nucleoside analogs than to nonnucleoside polymerase or protease inhibitors. Antimicrob Agents Chemother 52:1604–1612PubMedPubMedCentralCrossRefGoogle Scholar
  62. McCown MF, Rajyaguru S, Kular S et al (2009) GT-1a or GT-1b subtype-specific resistance profiles for hepatitis C virus inhibitors telaprevir and HCV-796. Antimicrob Agents Chemother 53:2129–2132PubMedPubMedCentralCrossRefGoogle Scholar
  63. Melnick JL, Crowther D, Barrera-Oro J (1961) Rapid development of drug-resistant mutants of poliovirus. Science 134:557PubMedCrossRefGoogle Scholar
  64. Menéndez-Arias L (2008) Mechanisms of resistance to nucleoside analogue inhibitors of HIV-1 reverse transcriptase. Virus Res 134:124–146PubMedCrossRefGoogle Scholar
  65. Menéndez-Arias L (2009) Mutation rates and intrinsic fidelity of retroviral reverse transcriptases. Viruses 1:1137–1165PubMedPubMedCentralCrossRefGoogle Scholar
  66. Menéndez-Arias L (2013) Molecular basis of human immunodeficiency virus type 1 drug resistance: overview and recent developments. Antiviral Res 98:93–120PubMedCrossRefGoogle Scholar
  67. Menéndez-Arias L, Álvarez M (2014) Antiretroviral therapy and drug resistance in human immunodeficiency virus type 2 infection. Antiviral Res 102:70–86PubMedCrossRefGoogle Scholar
  68. Menéndez-Arias L, Matamoros T, Cases-González CE (2006) Insertions and deletions in HIV-1 reverse transcriptase: consequences for drug resistance and viral fitness. Curr Pharm Des 12:1811–1825PubMedCrossRefGoogle Scholar
  69. Meyer PR, Matsuura SE, Mian AM et al (1999) A mechanism of AZT resistance: an increase in nucleotide-dependent primer unblocking by mutant HIV-1 reverse transcriptase. Mol Cell 4:35–43PubMedCrossRefGoogle Scholar
  70. Moreno H, Grande-Pérez A, Domingo E et al (2012) Arenaviruses and lethal mutagenesis. Prospects for new ribavirin-based interventions. Viruses 4:2786–2805PubMedPubMedCentralCrossRefGoogle Scholar
  71. Moreno E, Ojosnegros S, García-Arriaza J et al (2014) Exploration of sequence space as the basis of viral RNA genome segmentation. Proc Natl Acad Sci U S A 111:6678–6683PubMedPubMedCentralCrossRefGoogle Scholar
  72. Mullins JI, Heath L, Hughes JP et al (2011) Mutation of HIV-1 genomes in a clinical population treated with the mutagenic nucleoside KP1461. PLoS One 6:e15135PubMedPubMedCentralCrossRefGoogle Scholar
  73. Nakamoto S, Kanda T, Wu S et al (2014) Hepatitis C virus NS5A inhibitors and drug resistance mutations. World J Gastroenterol 20:2902–2912PubMedPubMedCentralCrossRefGoogle Scholar
  74. Nettles RE, Gao M, Bifano M et al (2011) Multiple ascending dose study of BMS-790052, a nonstructural protein 5A replication complex inhibitor, in patients infected with hepatitis C virus genotype 1. Hepatology 54:1956–1965PubMedCrossRefGoogle Scholar
  75. Neumann AU, Lam NP, Dahari H et al (1998) Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy. Science 282:103–107PubMedCrossRefGoogle Scholar
  76. Ojosnegros S, Perales C, Mas A et al (2011) Quasispecies as a matter of fact: viruses and beyond. Virus Res 162:203–215PubMedCrossRefGoogle Scholar
  77. Ortega-Prieto AM, Sheldon J, Grande-Pérez A et al (2013) Extinction of hepatitis C virus by ribavirin in hepatoma cells involves lethal mutagenesis. PLoS One 8:e71039PubMedPubMedCentralCrossRefGoogle Scholar
  78. Pawlotsky JM (2009) Therapeutic implications of hepatitis C virus resistance to antiviral drugs. Therap Adv Gastroenterol 2:205–219PubMedPubMedCentralCrossRefGoogle Scholar
  79. Pawlotsky JM (2014) What are the pros and cons of the use of host-targeted agents against hepatitis C? Antiviral Res 105:22–25PubMedCrossRefGoogle Scholar
  80. Pawlotsky JM, Germanidis G, Neumann AU et al (1998) Interferon resistance of hepatitis C virus genotype 1b: relationship to nonstructural 5A gene quasispecies mutations. J Virol 72:2795–2805PubMedPubMedCentralGoogle Scholar
  81. Perales C, Mateo R, Mateu MG et al (2007) Insights into RNA virus mutant spectrum and lethal mutagenesis events: replicative interference and complementation by multiple point mutants. J Mol Biol 369:985–1000PubMedCrossRefGoogle Scholar
  82. Perales C, Agudo R, Tejero H et al (2009) Potential benefits of sequential inhibitor-mutagen treatments of RNA virus infections. PLoS Pathog 5:e1000658PubMedPubMedCentralCrossRefGoogle Scholar
  83. Perales C, Iranzo J, Manrubia SC et al (2012) The impact of quasispecies dynamics on the use of therapeutics. Trends Microbiol 20:595–603PubMedCrossRefGoogle Scholar
  84. Perales C, Beach NM, Gallego I et al (2013) Response of hepatitis C virus to long-term passage in the presence of alpha interferon: multiple mutations and a common phenotype. J Virol 87:7593–7607PubMedPubMedCentralCrossRefGoogle Scholar
  85. Perales C, Beach NM, Sheldon J et al (2014) Molecular basis of interferon resistance in hepatitis C virus. Curr Opin Virol 8C:38–44CrossRefGoogle Scholar
  86. Perelson AS, Neumann AU, Markowitz M et al (1996) HIV-1 dynamics in vivo: virion clearance rate, infected cell life-span, and viral generation time. Science 271:1582–1586PubMedCrossRefGoogle Scholar
  87. Pfeiffer JK, Kirkegaard K (2005a) Increased fidelity reduces poliovirus fitness under selective pressure in mice. PLoS Pathog 1:102–110CrossRefGoogle Scholar
  88. Pfeiffer JK, Kirkegaard K (2005b) Ribavirin resistance in hepatitis C virus replicon-containing cell lines conferred by changes in the cell line or mutations in the replicon RNA. J Virol 79:2346–2355PubMedPubMedCentralCrossRefGoogle Scholar
  89. Poordad F, McCone J Jr, Bacon BR et al (2011) Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med 364:1195–1206PubMedPubMedCentralCrossRefGoogle Scholar
  90. Quer J, Martell A, Rodríguez R et al (2008) The impact of rapid evolution of hepatitis viruses. In: Domingo E, Parrish C, Holland JJ (eds) Origin and evolution of viruses. Elsevier, Oxford, pp 303–350CrossRefGoogle Scholar
  91. Raffi F, Rachlis A, Stellbrink HJ et al (2013) Once-daily dolutegravir versus raltegravir in antiretroviral-naive adults with HIV-1 infection: 48 week results from the randomised, double-blind, non-inferiority SPRING-2 study. Lancet 381:735–743PubMedCrossRefGoogle Scholar
  92. Richman DD (1996) Antiviral drug resistance. Wiley, New YorkGoogle Scholar
  93. Romano KP, Ali A, Royer WE et al (2010) Drug resistance against HCV NS3/4A inhibitors is defined by the balance of substrate recognition versus inhibitor binding. Proc Natl Acad Sci U S A 107:20986–20991PubMedPubMedCentralCrossRefGoogle Scholar
  94. Sarrazin C, Zeuzem S (2010) Resistance to direct antiviral agents in patients with hepatitis C virus infection. Gastroenterology 138:447–462PubMedCrossRefGoogle Scholar
  95. Sarrazin C, Kieffer TL, Bartels D et al (2007) Dynamic hepatitis C virus genotypic and phenotypic changes in patients treated with the protease inhibitor telaprevir. Gastroenterology 132:1767–1777PubMedCrossRefGoogle Scholar
  96. Seiler P, Senn BM, Klenerman P et al (2000) Additive effect of neutralizing antibody and antiviral drug treatment in preventing virus escape and persistence. J Virol 74:5896–5901PubMedPubMedCentralCrossRefGoogle Scholar
  97. Serre SB, Krarup HB, Bukh J et al (2013) Identification of alpha interferon-induced envelope mutations of hepatitis C virus in vitro associated with increased viral fitness and interferon resistance. J Virol 87:12776–12793PubMedPubMedCentralCrossRefGoogle Scholar
  98. Sheldon J, Beach NM, Moreno E et al (2014) Increased replicative fitness can lead to decreased drug sensitivity of hepatitis C virus. J Virol 88:12098–12111PubMedPubMedCentralCrossRefGoogle Scholar
  99. Shiffman ML (2008) Optimizing the current therapy for chronic hepatitis C virus: peginterferon and ribavirin dosing and the utility of growth factors. Clin Liver Dis 12:487–505, viiPubMedCrossRefGoogle Scholar
  100. Shirasaka T, Kavlick MF, Ueno T et al (1995) Emergence of human immunodeficiency virus type 1 variants with resistance to multiple dideoxynucleosides in patients receiving therapy with dideoxynucleosides. Proc Natl Acad Sci U S A 92:2398–2402PubMedPubMedCentralCrossRefGoogle Scholar
  101. Shirogane Y, Watanabe S, Yanagi Y (2012) Cooperation between different RNA virus genomes produces a new phenotype. Nat Commun 3:1235PubMedCrossRefGoogle Scholar
  102. Sofia MJ, Bao D, Chang W et al (2010) Discovery of a beta-d-2'-deoxy-2'-alpha-fluoro-2'-beta-C-methyluridine nucleotide prodrug (PSI-7977) for the treatment of hepatitis C virus. J Med Chem 53:7202–7218PubMedCrossRefGoogle Scholar
  103. Sostegni R, Ghisetti V, Pittaluga F et al (1998) Sequential versus concomitant administration of ribavirin and interferon alfa-n3 in patients with chronic hepatitis C not responding to interferon alone: results of a randomized, controlled trial. Hepatology 28:341–346PubMedCrossRefGoogle Scholar
  104. Sulkowski MS, Gardiner DF, Rodriguez-Torres M et al (2014) Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection. N Engl J Med 370:211–221PubMedCrossRefGoogle Scholar
  105. Summa V, Ludmerer SW, McCauley JA et al (2012) MK-5172, a selective inhibitor of hepatitis C virus NS3/4a protease with broad activity across genotypes and resistant variants. Antimicrob Agents Chemother 56:4161–4167PubMedPubMedCentralCrossRefGoogle Scholar
  106. Susser S, Welsch C, Wang Y et al (2009) Characterization of resistance to the protease inhibitor boceprevir in hepatitis C virus-infected patients. Hepatology 50:1709–1718PubMedCrossRefGoogle Scholar
  107. Susser S, Vermehren J, Forestier N et al (2011) Analysis of long-term persistence of resistance mutations within the hepatitis C virus NS3 protease after treatment with telaprevir or boceprevir. J Clin Virol 52:321–327PubMedCrossRefGoogle Scholar
  108. Swetina J, Schuster P (1982) Self-replication with errors. A model for polynucleotide replication. Biophys Chem 16:329–345PubMedCrossRefGoogle Scholar
  109. Teng MN, Oldstone MB, de la Torre JC (1996) Suppression of lymphocytic choriomeningitis virus-induced growth hormone deficiency syndrome by disease-negative virus variants. Virology 223:113–119PubMedCrossRefGoogle Scholar
  110. Thompson AJ, Locarnini SA, Beard MR (2011) Resistance to anti-HCV protease inhibitors. Curr Opin Virol 1:599–606PubMedCrossRefGoogle Scholar
  111. Tong X, Le Pogam S, Li L et al (2014) In vivo emergence of a novel mutant L159F/L320F in the NS5B polymerase confers low-level resistance to the HCV polymerase inhibitors mericitabine and sofosbuvir. J Infect Dis 209:668–675PubMedCrossRefGoogle Scholar
  112. Tsibris AM, Korber B, Arnaout R et al (2009) Quantitative deep sequencing reveals dynamic HIV-1 escape and large population shifts during CCR5 antagonist therapy in vivo. PLoS One 4:e5683PubMedPubMedCentralCrossRefGoogle Scholar
  113. Tu X, Das K, Han Q et al (2010) Structural basis of HIV-1 resistance to AZT by excision. Nat Struct Mol Biol 17:1202–1209PubMedPubMedCentralCrossRefGoogle Scholar
  114. Vignuzzi M, Andino R (2010) Biological implications of picornavirus fidelity mutants. In: Ehrenfeld E, Domingo E, Roos RP (eds) The picornaviruses. ASM Press, Washington, DC, pp 213–228CrossRefGoogle Scholar
  115. Vignuzzi M, Stone JK, Arnold JJ et al (2006) Quasispecies diversity determines pathogenesis through cooperative interactions in a viral population. Nature 439:344–348PubMedCrossRefGoogle Scholar
  116. Vignuzzi M, Wendt E, Andino R (2008) Engineering attenuated virus vaccines by controlling replication fidelity. Nat Med 14:154–161PubMedCrossRefGoogle Scholar
  117. von Kleist M, Menz S, Stocker H et al (2011) HIV quasispecies dynamics during pro-active treatment switching: impact on multi-drug resistance and resistance archiving in latent reservoirs. PLoS One 6:e18204CrossRefGoogle Scholar
  118. Wainberg MA, Mesplede T, Raffi F (2013) What if HIV were unable to develop resistance against a new therapeutic agent? BMC Med 11:249PubMedPubMedCentralCrossRefGoogle Scholar
  119. Webster RG, Kawaoka Y, Bean WJ (1986) Vaccination as a strategy to reduce the emergence of amantadine- and rimantadine-resistant strains of A/Chick/Pennsylvania/83 (H5N2) influenza virus. J Antimicrob Chemother 18:157–164PubMedCrossRefGoogle Scholar
  120. Wensing AM, Calvez V, Günthard HF et al (2014) 2014 Update of the drug resistance mutations in HIV-1. Top Antivir Med 22:642–650PubMedPubMedCentralGoogle Scholar
  121. Westby M, Lewis M, Whitcomb J et al (2006) Emergence of CXCR4-using human immunodeficiency virus type 1 (HIV-1) variants in a minority of HIV-1-infected patients following treatment with the CCR5 antagonist maraviroc is from a pretreatment CXCR4-using virus reservoir. J Virol 80:4909–4920PubMedPubMedCentralCrossRefGoogle Scholar
  122. Westby M, Smith-Burchnell C, Mori J et al (2007) Reduced maximal inhibition in phenotypic susceptibility assays indicates that viral strains resistant to the CCR5 antagonist maraviroc utilize inhibitor-bound receptor for entry. J Virol 81:2359–2371PubMedCrossRefGoogle Scholar
  123. Wyles DL (2013) Antiviral resistance and the future landscape of hepatitis C virus infection therapy. J Infect Dis 207(Suppl 1):S33–S39PubMedCrossRefGoogle Scholar
  124. Young KC, Lindsay KL, Lee KJ et al (2003) Identification of a ribavirin-resistant NS5B mutation of hepatitis C virus during ribavirin monotherapy. Hepatology 38:869–878PubMedCrossRefGoogle Scholar
  125. Zeuzem S, Andreone P, Pol S et al (2011) Telaprevir for retreatment of HCV infection. N Engl J Med 364:2417–2428PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Celia Perales
    • 1
    • 2
    Email author
  • Ana M. Ortega-Prieto
    • 1
  • Nathan M. Beach
    • 1
  • Julie Sheldon
    • 1
    • 3
  • Luis Menéndez-Arias
    • 1
  • Esteban Domingo
    • 1
    • 2
  1. 1.Centro de Biología Molecular “Severo Ochoa” (CSIC-UAM)Consejo Superior de Investigaciones Científicas (CSIC)MadridSpain
  2. 2.Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd)BarcelonaSpain
  3. 3.Division of Experimental Virology, TwincoreCentre for Experimental and Clinical Infection Research, a joint venture between Medical School Hannover and Helmholtz Centre for Infection ResearchHannoverGermany

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