Skip to main content
SpringerLink
Log in

Antiviral Resistance and Impact on Viral Replication Capacity: Evolution of Viruses Under Antiviral Pressure Occurs in Three Phases

  • Chapter
Antiviral Strategies

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 189))

Resistance development is a major obstacle to antiviral therapy, and all active antiviral agents have shown to select for resistance mutations. Aspects of antiviral resistance development are discussed for specific compounds or drug classes in the previous chapters, while this chapter provides an overview regarding the evolution of different viruses (HIV, HBV, HCV, and Influenza) under pressure of antiviral therapy. Virus replication is an error prone process resulting in a large number of variants (quasispecies) in patients. Resistance evolution under suboptimal therapy can be schematically distinguished into three phases. (1) preexisting variants less sensitive to the respective drug are selected from the quasispecies population, (2) outgrowing variants acquire additional mutations increasing their resistance, and (3) compensatory mutations accumulate to overcome the generally reduced replica-tive capacity of resistant variants. Successful therapy should be aimed at suppression of all existing viral variants, thus preventing selection of minority species and their subsequent evolution. This implies that the amount of mutations required for first escape to the viral regimen (genetic barrier) should be larger than the expected number of mutations present in viruses in the quasispecies. Accordingly, combination therapy can achieve complete inhibition of replication for most HIV, HBV, and Influenza infected patients without resistance development. However, resistant viruses can become selected under circumstances of suboptimal antiviral therapy and these resistant viruses can be transmitted. Proper use of drugs and worldwide monitoring for the presence and spread of drug resistant viruses are therefore of utmost importance.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Abed Y, Goyette N, Boivin G (2005) Generation and characterization of recombinant influenza A (H1N1) viruses harboring amantadine resistance mutations. Antimicrob Agents Chemother 49:556–559

    Article  PubMed  CAS  Google Scholar 

  • Abed Y, Baz M, Boivin G (2006) Impact of neuraminidase mutations conferring influenza resistance to neuraminidase inhibitors in the N1 and N2 genetic backgrounds. Antivir Ther 11:971–976

    PubMed  CAS  Google Scholar 

  • Aoki FY, Boivin G, Roberts N (2007) Influenza virus susceptibility and resistance to oseltamivir. Antivir Ther 12:603–616

    PubMed  CAS  Google Scholar 

  • Arion D, Kaushik N, McCormick S, Borkow G, Parniak MA (1998) Phenotypic mechanism of HIV-1 resistance to 3′-azido-3′-deoxythymidine (AZT): increased polymerization processivity and enhanced sensitivity to pyrophosphate of the mutant viral reverse transcriptase. Biochem 37:15908–15917

    Article  CAS  Google Scholar 

  • Bartholomeusz A, Locarnini S (2006) Hepatitis B virus mutations associated with antiviral therapy J Med Virol 78 Suppl 1:S52–S55

    Article  PubMed  CAS  Google Scholar 

  • Borroto-Esoda K, Miller MD, Arterburn S (2007) Pooled analysis of amino acid changes in the HBV polymerase in patients from four major adefovir dipivoxil clinical trials. J Hepatol 47:492–498

    Article  CAS  Google Scholar 

  • Bright RA, Medina MJ, Xu X, Perez-Oronoz G, Wallis TR, Davis XM, Povinelli L, Cox NJ,Klimov AI (2005) Incidence of adamantane resistance among influenza A (H3N2) viruses isolated worldwide from 1994 to 2005: a cause for concern. Lancet 366:1175–1181

    Article  PubMed  CAS  Google Scholar 

  • Bright RA, Shay DK, Shu B, Cox NJ, Klimov AI (2006) Adamantane resistance among influenza A viruses isolated early during the 2005–2006 influenza season in the United States. JAMA 295:891–894

    Article  PubMed  CAS  Google Scholar 

  • Coffin JM (1995) HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy. Science 267:483–489

    Article  PubMed  CAS  Google Scholar 

  • Colonno RJ, Rose R, Baldick CJ, Levine S, Pokornowski K, Yu CF, Walsh A, Fang J, Hsu M, Mazzucco C, Eggers B, Zhang S, Plym M, Klesczewski K, Tenney DJ (2006) Entecavir resistance is rare in nucleoside naive patients with hepatitis B. Hepatology 44:1656–1665

    Article  PubMed  CAS  Google Scholar 

  • Das K, Xiong X, Yang H, Westland CE, Gibbs CS, Sarafianos SG, Arnold E (2001) Molecular modeling and biochemical characterization reveal the mechanism of hepatitis B virus polymerase resistance to lamivudine (3TC) and emtricitabine (FTC). J Virol 75:4771–4779

    Article  PubMed  CAS  Google Scholar 

  • De FR, Migliaccio G (2005) Challenges and successes in developing new therapies for hepatitis C. Nature 436:953–960

    Article  CAS  Google Scholar 

  • de Jong MD, Schuurman R, Lange JMA, Boucher CAB (1996) Replication of a pre-existing resistant HIV-1 subpopulation in vivo after introduction of a strong selective drug pressure. Antivir Ther 1:33–41

    PubMed  Google Scholar 

  • de Jong MD, Tran TT, Truong HK, Vo MH, Smith GJ, Nguyen VC, Bach VC, Phan TQ, Do QH, Guan Y, Peiris JS, Tran TH, Farrar J (2005) Oseltamivir resistance during treatment of influenza A (H5N1) infection. N Engl J Med 353:2667–2672

    Article  PubMed  Google Scholar 

  • De Meyer S, Azijn H, Surleraux D, Jochmans D, Tahri A, Pauwels R, Wigerinck P, de Bethune MP (2005) TMC114, a novel human immunodeficiency virus type 1 protease inhibitor active against protease inhibitor-resistant viruses, including a broad range of clinical isolates. Antimicrob Agents Chemother 49:2314–2321

    Article  PubMed  CAS  Google Scholar 

  • Delaney WE, Yang H, Westland CE, Das K, Arnold E, Gibbs CS, Miller MD, Xiong S (2003) The hepatitis B virus polymerase mutation rtV173L is selected during lamivudine therapy and enhances viral replication in vitro. J Virol 77:11833–11841

    Article  PubMed  CAS  Google Scholar 

  • Delwart EL, Sheppard HW, Walker BD, Goudsmit J, Mullins JI (1994) Human immunodeficiency virus type 1 evolution in vivo tracked by DNA heteroduplex mobility assays. J Virol 68:6672–6683

    PubMed  CAS  Google Scholar 

  • Delwart EL, Pan H, Neumann A, Markowitz M (1998) Rapid, transient changes at the env locus of plasma Human Immunodeficiency Virus type 1 populations during the emergence fo protease inhibitor resistance. J Virol 72:2416–2421

    PubMed  CAS  Google Scholar 

  • Dierynck I, De WM, Gustin E, Keuleers I, Vandersmissen J, Hallenberger S, Hertogs K (2007) Binding kinetics of darunavir to human immunodeficiency virus type 1 protease explain the potent antiviral activity and high genetic barrier. J Virol 81:13845–13851

    Article  PubMed  CAS  Google Scholar 

  • Domingo E, Menendez Arias L, Quinones-Mateu ME, Holguin A, Gutierrez-Rivas M, Martinez MA, Quer J, Novella IS, Holland JJ (1997) Viral quasispecies and the problem of vaccine-escape and drug-resistant mutants. Prog Drug Res 48:99–128

    PubMed  CAS  Google Scholar 

  • Doyon L, Croteau G, Thibeault D, Poulin F, Pilote L, Lamarre D (1996) Second locus involved in human immunodeficiency virus type 1 resistance to protease inhibitors. J Virol 70:3763–3769

    PubMed  CAS  Google Scholar 

  • Doyon L, Payant C, Brakier Gingras L, Lamarre D (1998) Novel Gag-Pol frameshift site in human immunodeficiency virus type 1 variants resistant to protease inhibitors. J Virol 72:6146–6150

    PubMed  CAS  Google Scholar 

  • Durantel D, Brunelle MN, Gros E, Carrouee-Durantel S, Pichoud C, Villet S, Trepo C, Zoulim F (2005) Resistance of human hepatitis B virus to reverse transcriptase inhibitors: from genotypic to phenotypic testing. J Clin Virol 34 Suppl 1:S34–S43

    Article  PubMed  CAS  Google Scholar 

  • Ferraris O, Lina B (2008) Mutations of neuraminidase implicated in neuraminidase inhibitors resistance. J Clin Virol 41:13–19

    Article  PubMed  CAS  Google Scholar 

  • Gallant JE, Rodriguez AE, Weinberg WG, Young B, Berger DS, Lim ML, Liao Q, Ross L, Johnson J, Shaefer MS (2005) Early virologic nonresponse to tenofovir, abacavir, and lamivu-dine in HIV-infected antiretroviral-naive subjects. J Infect Dis 192:1921–1930

    Article  PubMed  CAS  Google Scholar 

  • Garcia-Lerma JG, MacInnes H, Bennett D, Weinstock H, Heneine W (2004) Transmitted human immunodeficiency virus type 1 carrying the D67N or K219Q/E mutation evolves rapidly to zidovudine resistance in vitro and shows a high replicative fitness in the presence of zidovudine. J Virol 78:7545–7552

    Article  PubMed  CAS  Google Scholar 

  • Gubareva LV, Kaiser L, Matrosovich MN, Soo-Hoo Y, Hayden FG (2001) Selection of influenza virus mutants in experimentally infected volunteers treated with oseltamivir. J Infect Dis 183:523–531

    Article  PubMed  CAS  Google Scholar 

  • Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, Chang TT, Kitis G, Rizzetto M, Marcellin P, Lim SG, Goodman Z, Ma J, Brosgart CL, Borroto-Esoda K, Arterburn S, Chuck SL (2006) Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years. Gastroenterology 131:1743–1751

    Article  PubMed  CAS  Google Scholar 

  • Hayden FG (2006) Antivirals for influenza: historical perspectives and lessons learned. Antiviral Res 71:372–378

    Article  PubMed  CAS  Google Scholar 

  • Hayden FG, Belshe RB, Clover RD, Hay AJ, Oakes MG, Soo W (1989) Emergence and apparent transmission of rimantadine-resistant influenza A virus in families. N Engl J Med 321:1696–1702

    PubMed  CAS  Google Scholar 

  • Hazuda DJ, Miller MD, Nguyen BN, Zhao J, for the P005 study team (2007) Resistance to HIV- integrase inhibitor raltegravir: analysis of protocol 005, a Phase II study in patients with triple-class resistant HIV-1 infection. Antivir Ther 12:S10

    Google Scholar 

  • Herlocher ML, Truscon R, Elias S, Yen HL, Roberts NA, Ohmit SE, Monto AS (2004) Influenza viruses resistant to the antiviral drug oseltamivir: transmission studies in ferrets. J Infect Dis 190:1627–1630

    Article  PubMed  CAS  Google Scholar 

  • Hertogs K, de Bethune MP, Miller V, Ivens T, Schel P, Van Cauwenberge A, Van Den Eynde C, Van Gerwen V, Azijn H, Van Houtte M, Peeters F, Staszewski S, Conant M, Bloor S, Kemp S, Larder B, Pauwels R (1998) A rapid method for simultaneous detection of phenotypic resistance to inhibitors of protease and reverse transcriptase in recombinant human immunodeficiency virus type 1 isolates from patients treated with antiretroviral drugs. Antimicrob Agents Chemother 42:269–276

    Article  PubMed  CAS  Google Scholar 

  • Howe AY, Cheng H, Thompson I, Chunduru SK, Herrmann S, O'Connell J, Agarwal A, Chopra R, Del Vecchio AM (2006) Molecular mechanism of a thumb domain hepatitis C virus nonnucleo-side RNA-dependent RNA polymerase inhibitor. Antimicrob Agents Chemother 50:4103–4113

    Article  PubMed  CAS  Google Scholar 

  • Hsiou Y, Ding J, Das K, Clark AD Jr, Boyer PL, Lewi P, Janssen PA, Kleim JP, Rosner M, Hughes SH, Arnold E (2001) The Lys103Asn mutation of HIV-1 RT: a novel mechanism of drug resistance. J Mol Biol 309:437–445

    Article  PubMed  CAS  Google Scholar 

  • Huigen MC, van Ham PM, de GL, Kagan RM, Boucher CA, Nijhuis M (2008) Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. Retrovirology 5:20

    Article  PubMed  CAS  Google Scholar 

  • Ives JA, Carr JA, Mendel DB, Tai CY, Lambkin R, Kelly L, Oxford JS, Hayden FG, Roberts NA (2002) The H274Y mutation in the influenza A/H1N1 neuraminidase active site following oseltamivir phosphate treatment leave virus severely compromised both in vitro and in vivo. Antiviral Res 55:307–317

    Article  PubMed  CAS  Google Scholar 

  • Jourdain G, Ngo-Giang-Huong N, Le CS, Bowonwatanuwong C, Kantipong P, Leechanachai P, Ariyadej S, Leenasirimakul P, Hammer S, Lallemant M (2004) Intrapartum exposure to nevi- rapine and subsequent maternal responses to nevirapine-based antiretroviral therapy. N Engl J Med 351:229–240

    Article  PubMed  CAS  Google Scholar 

  • Kantor R (2006) Impact of HIV-1 pol diversity on drug resistance and its clinical implications. Curr Opin Infect Dis 19:594–606

    Article  PubMed  CAS  Google Scholar 

  • King NM, Melnick L, Prabu-Jeyabalan M, Nalivaika EA, Yang SS, Gao Y, Nie X, Zepp C, Heefner DL, Schiffer CA (2002) Lack of synergy for inhibitors targeting a multi-drug-resistant HIV-1protease. Protein Sci 11:418–429

    Article  PubMed  CAS  Google Scholar 

  • Kiso M, Mitamura K, Sakai-Tagawa Y, Shiraishi K, Kawakami C, Kimura K, Hayden FG, Sugaya N, Kawaoka Y (2004) Resistant influenza A viruses in children treated with oseltamivir: descriptive study. Lancet 364:759–765

    Article  PubMed  CAS  Google Scholar 

  • Kleim JP, Rösner M, Winkler I, Paessens A, Kirsch R, Hsiou Y, Arnolds E, Riess G (1996) Selective pressure of a quinoxaline nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) on HIV-1 replication results in the emergence of nucleoside RT-inhibitor-specific (RT Leu-74 -> Val or Ile and Val-75 - > Leu or Ile) HIV-1 mutants. Proc Natl Acad Sci USA 93:34–38

    Article  PubMed  CAS  Google Scholar 

  • Kukolj G, McGibbon GA, McKercher G, Marquis M, Lefebvre S, Thauvette L, Gauthier J, Goulet S, Poupart MA, Beaulieu PL (2005) Binding site characterization and resistance to a class of non-nucleoside inhibitors of the hepatitis C virus NS5B polymerase. J Biol Chem 280:39260–39267

    Article  PubMed  CAS  Google Scholar 

  • Labrosse B, Morand-Joubert L, Goubard A, Rochas S, Labernardiere JL, Pacanowski J, Meynard JL, Hance AJ, Clavel F, Mammano F (2006) Role of the envelope genetic context in the development of enfuvirtide resistance in human immunodeficiency virus type 1-infected patients. J Virol 80:8807–8819

    Article  PubMed  CAS  Google Scholar 

  • Lai CL, Gane E, Liaw YF, Hsu CW, Thongsawat S, Wang Y, Chen Y, Heathcote EJ, Rasenack J, Bzowej N, Naoumov NV, di Bisceglie AM, Zeuzem S, Moon YM, Goodman Z, Chao G, Constance BF, Brown NA (2007) Telbivudine versus lamivudine in patients with chronic hepatitis B. N Engl J Med 357:2576–2588

    Article  PubMed  CAS  Google Scholar 

  • Landman R, Descamps D, Peytavin G, Trylesinski A, Katlama C, Girard PM, Bonnet B, Yeni P, Bentata M, Michelet C, Benalycherif A, Brun VF, Miller MD, Flandre P (2005) Early virologic failure and rescue therapy of tenofovir, abacavir, and lamivudine for initial treatment of HIV-1 infection: TONUS study. HIV Clin Trials 6:291–301

    Article  PubMed  CAS  Google Scholar 

  • Lanier ER, Hazen R, Ross L, Freeman A, Harvey R (2005) Lack of antagonism between abacavir, lamivudine, and tenofovir against wild-type and drug-resistant HIV-1. J Acquir Immune Defic Syndr 39:519–522

    PubMed  CAS  Google Scholar 

  • Le PS, Jiang WR, Leveque V, Rajyaguru S, Ma H, Kang H, Jiang S, Singer M, Ali S, Klumpp K, Smith D, Symons J, Cammack N, Najera I (2006a) In vitro selected Con1 subgenomic replicons resistant to 2′-C-methyl-cytidine or to R1479 show lack of cross resistance. Virol 351:349–359

    Article  CAS  Google Scholar 

  • Le PS, Kang H, Harris SF, Leveque V, Giannetti AM, Ali S, Jiang WR, Rajyaguru S, Tavares G, Oshiro C, Hendricks T, Klumpp K, Symons J, Browner MF, Cammack N, Najera I (2006b) Selection and characterization of replicon variants dually resistant to thumb- and palm-binding nonnucleoside polymerase inhibitors of the hepatitis C virus. J Virol 80:6146–6154

    Article  CAS  Google Scholar 

  • Lecossier D, Shulman NS, Morand-Joubert L, Shafer RW, Joly V, Zolopa AR, Clavel F, Hance AJ (2005) Detection of minority populations of HIV-1 expressing the K103N resistance mutation in patients failing nevirapine. J Acquir Immune Defic Syndr 38:37–42

    Article  PubMed  CAS  Google Scholar 

  • Leigh Brown AJ (1997) Analysis of HIV-1 env gene sequences reveals evidence for a low effective number in the viral population. Proc Natl Acad Sci USA 94:1862–1865

    Article  Google Scholar 

  • Leigh Brown AJ, Richman DD (1997) HIV-1: gambling on the evolution of drug resistance? Nat Med 3:268–271

    Article  CAS  Google Scholar 

  • Lin K, Hazuda D, Otto M, Boucher C, Schooley R, O'Rear J, Kempf D, Kwong A, Parkin N, for the HCV Drug Resistance Advisory Group (2007) Initial recommendations for HCV drug resistance analysis: a consensus statement from the HCV Drug Resistance Advisory Group. Glob Antivir J 3:29

    Google Scholar 

  • Lindenbach BD, Rice CM (2005) Unravelling hepatitis C virus replication from genome to function. Nature 436:933–938

    Article  PubMed  CAS  Google Scholar 

  • Locarnini S, Mason WS (2006) Cellular and virological mechanisms of HBV drug resistance. J Hepatol 44:422–431

    Article  PubMed  CAS  Google Scholar 

  • Lockman S, Shapiro RL, Smeaton LM, Wester C, Thior I, Stevens L, Chand F, Makhema J, Moffat C, Asmelash A, Ndase P, Arimi P, van WE, Mazhani L, Novitsky V, Lagakos S, Essex M (2007) Response to antiretroviral therapy after a single, peripartum dose of nevirapine. N Engl J Med 356:135–147

    Article  PubMed  CAS  Google Scholar 

  • Lok AS, Zoulim F, Locarnini S, Bartholomeusz A, Ghany MG, Pawlotsky JM, Liaw YF, Mizokami M, Kuiken C (2007) Antiviral drug-resistant HBV: standardization of nomenclature and assays and recommendations for management. Hepatology 46:254–265

    Article  PubMed  CAS  Google Scholar 

  • Lu L, Dekhtyar T, Masse S, Pithawalla R, Krishnan P, He W, Ng T, Koev G, Stewart K, Larson D, Bosse T, Wagner R, Pilot-Matias T, Mo H, Molla A (2007) Identification and characterization of mutations conferring resistance to an HCV RNA-dependent RNA polymerase inhibitor in vitro. Antiviral Res 76:93–97

    Article  PubMed  CAS  Google Scholar 

  • Luber AD (2005) Genetic barriers to resistance and impact on clinical response. MedGenMed 7:69

    PubMed  Google Scholar 

  • Maguire MF, Guinea R, Griffin P, Macmanus S, Elston RC, Wolfram J, Richards N, Hanlon MH, Porter DJ, Wrin T, Parkin N, Tisdale M, Furfine E, Petropoulos C, Snowden BW, Kleim JP (2002)Changes in human immunodeficiency virus type 1 Gag at positions L449 and P453 are linked to I50V protease mutants in vivo and cause reduction of sensitivity to amprenavir and improved viral fitness in vitro. J Virol 76:7398–7406

    Article  PubMed  CAS  Google Scholar 

  • Mammano F, Petit C, Clavel F (1998) Resistance-associated loss of viral fitness in human immunodeficiency virus type 1: phenotypic analysis of protease and gag coevolution in protease inhibitor-treated patients. J Virol 72:7632–7637

    PubMed  CAS  Google Scholar 

  • Manns MP, Foster GR, Rockstroh JK, Zeuzem S, Zoulim F, Houghton M (2007) The way forward in HCV treatment–finding the right path. Nat Rev Drug Discov 6:991–1000

    Article  PubMed  CAS  Google Scholar 

  • Meyer PR, Matsuura SE, Mohsin Mian A, So AG, Scott WA (1999) A mechanism of AZT resistance: an increase in nucleotide-dependent primer unblocking by mutant HIV-1 reverse tran-scriptase. Mol Cell 4:35–43

    Article  PubMed  CAS  Google Scholar 

  • Migliaccio G, Tomassini JE, Carroll SS, Tomei L, Altamura S, Bhat B, Bartholomew L, Bosserman MR, Ceccacci A, Colwell LF, Cortese R, De FR, Eldrup AB, Getty KL, Hou XS, LaFemina RL, Ludmerer SW, MacCoss M, McMasters DR, Stahlhut MW, Olsen DB, Hazuda DJ, Flores OA (2003)Characterization of resistance to non-obligate chain-terminating ribonucleoside analogs that inhibit hepatitis C virus replication in vitro. J Biol Chem 278:49164–49170

    Article  PubMed  CAS  Google Scholar 

  • Mink M, Mosier SM, Janumpalli S, Davison D, Jin L, Melby T, Sista P, Erickson J, Lambert D, Stanfield-Oakley SA, Salgo M, Cammack N, Matthews T, Greenberg ML (2005) Impact of human immunodeficiency virus type 1 gp41 amino acid substitutions selected during enfuvirtide treatment on gp41 binding and antiviral potency of enfuvirtide in vitro. J Virol 79:12447–12454

    Article  PubMed  CAS  Google Scholar 

  • Mo H, Lu L, Pilot-Matias T, Pithawalla R, Mondal R, Masse S, Dekhtyar T, Ng T, Koev G, Stoll V, Stewart KD, Pratt J, Donner P, Rockway T, Maring C, Molla A (2005) Mutations conferring resistance to a hepatitis C virus (HCV) RNA-dependent RNA polymerase inhibitor alone or in combination with an HCV serine protease inhibitor in vitro. Antimicrob Agents Chemother 49:4305–4314

    Article  PubMed  CAS  Google Scholar 

  • Najera I, Richman DD, Olivares I, Rojas JM, Peinado MA, Perucho M, Najera R, Lopez Galindez C (1994) Natural occurrence of drug resistance mutations in the reverse transcriptase of human immunodeficiency virus type 1 isolates. AIDS Res Hum Retroviruses 10:1479–1488

    Article  PubMed  CAS  Google Scholar 

  • Nijhuis M, Boucher CAB, Schipper P, Leitner T, Schuurman R, Albert J (1998) Stochastic processes strongly influence HIV-1 evolution during suboptimal protease inhibitor therapy. Proc Natl Acad Sci USA 95:14441–14446

    Article  PubMed  CAS  Google Scholar 

  • Nijhuis M, Schuurman R, de Jong D, Erickson J, Gustchina E, Albert J, Schipper P, Gulnik S, Boucher CAB (1999) Increased fitness of drug resistant HIV-1 protease as a result of acquisition of compensatory mutations during suboptimal therapy. AIDS 13:2349–2359

    Article  PubMed  CAS  Google Scholar 

  • Nijhuis M, van Maarseveen NM, Lastere S, Schipper P, Coakley E, Glass B, Rovenska M, de JD, Chappey C, Goedegebuure IW, Heilek-Snyder G, Dulude D, Cammack N, Brakier-Gingras L, Konvalinka J, Parkin N, Krausslich HG, Brun-Vezinet F, Boucher CA (2007) A novel substrate-based HIV-1 protease inhibitor drug resistance mechanism. PLoS Med 4:e36

    Article  PubMed  CAS  Google Scholar 

  • Ono SK, Kato N, Shiratori Y, Kato J, Goto T, Schinazi RF, Carrilho FJ, Omata M (2001) The poly- merase L528M mutation cooperates with nucleotide binding-site mutations, increasing hepatitis B virus replication and drug resistance. J Clin Invest 107:449–455

    Article  PubMed  CAS  Google Scholar 

  • Pawlotsky JM, Chevaliez S, McHutchison JG (2007) The hepatitis C virus life cycle as a target for new antiviral therapies. Gastroenterology 132:1979–1998

    Article  PubMed  CAS  Google Scholar 

  • Petropoulos CJ, Parkin NT, Limoli KL, Lie YS, Wrin T, Huang W, Tian H, Smith D, Winslow GA, Capon DJ, Whitcomb JM (2000) A novel phenotypic drug susceptibility assay for HIV-1. Antim Ag Chemoth 44:920–928

    Article  CAS  Google Scholar 

  • Podzamczer D, Ferrer E, Gatell JM, Niubo J, Dalmau D, Leon A, Knobel H, Polo C, Iniguez D, Ruiz I (2005) Early virological failure with a combination of tenofovir, didanosine and efavirenz. Antivir Ther 10:171–177

    PubMed  CAS  Google Scholar 

  • Prado JG, Wrin T, Beauchaine J, Ruiz L, Petropoulos CJ, Frost SD, Clotet B, D'Aquila RT, Martinez-Picado J (2002) Amprenavir-resistant HIV-1 exhibits lopinavir cross-resistance and reduced replication capacity. AIDS 16:1009–1017

    Article  PubMed  CAS  Google Scholar 

  • Quinones-Mateu ME, Arts EJ (2001) HIV-1 fitness: implications for drug resistance, disease progression an global epidemic evolution. In: Kuiken C, Foley B, Hahn B, Marx PA, McCutchan F, Mellors J (eds) HIV sequence compendium 2001. Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM

    Google Scholar 

  • Rameix-Welti MA, Agou F, Buchy P, Mardy S, Aubin JT, Veron M, van der WS, Naffakh N (2006) Natural variation can significantly alter the sensitivity of influenza A (H5N1) viruses to oseltamivir. Antimicrob Agents Chemother 50:3809–3815

    Article  PubMed  CAS  Google Scholar 

  • Ruane PJ, DeJesus E (2004) New nucleoside/nucleotide backbone options: a review of recent studies. J Acquir Immune Defic Syndr 37 Suppl 1:S21–S29

    PubMed  CAS  Google Scholar 

  • Sarafianos SG, Das K, Clark AD Jr, Ding J, Boyer PL, Hughes SH, Arnold E (1999) Lamivu-dine (3TC) resistance in HIV-1 reverse transcriptase involves steric hindrance with β-branched amino acids. Proc Natl Acad Sci USA 96:10027–10032

    Article  PubMed  CAS  Google Scholar 

  • Sarrazin C, Kieffer TL, Bartels D, Hanzelka B, Muh U, Welker M, Wincheringer D, Zhou Y, Chu HM, Lin C, Weegink C, Reesink H, Zeuzem S, Kwong AD (2007) Dynamic hepatitis C virus genotypic and phenotypic changes in patients treated with the protease inhibitor telaprevir. Gastroenterology 132:1767–1777

    Article  PubMed  CAS  Google Scholar 

  • Shaw T, Bartholomeusz A, Locarnini S (2006) HBV drug resistance: mechanisms, detection and interpretation. J Hepatol 44:593–606

    Article  PubMed  CAS  Google Scholar 

  • Sheldon J, Rodes B, Zoulim F, Bartholomeusz A, Soriano V (2006) Mutations affecting the replication capacity of the hepatitis B virus. J Viral Hepat 13:427–434

    Article  PubMed  CAS  Google Scholar 

  • SPREAD Programme (2008) Transmission of drug-resistant HIV-1 in Europe remains limited to single classes. AIDS 22:625–635

    Google Scholar 

  • Staschke KA, Colacino JM, Baxter AJ, Air GM, Bansal A, Hornback WJ, Munroe JE, Laver WG (1995) Molecular basis for the resistance of influenza viruses to 4-guanidino-Neu5Ac2en. Virol 214:642–646

    Article  CAS  Google Scholar 

  • Tai CY, Escarpe PA, Sidwell RW, Williams MA, Lew W, Wu H, Kim CU, Mendel DB (1998) Characterization of human influenza virus variants selected in vitro in the presence of the neu-raminidase inhibitor GS 4071. Antimicrob Agents Chemother 42:3234–3241

    PubMed  CAS  Google Scholar 

  • Thomson MM, Najera R (2005) Molecular epidemiology of HIV-1 variants in the global AIDS pandemic: an update. AIDS Rev 7:210–224

    PubMed  Google Scholar 

  • Tomei L, Altamura S, Bartholomew L, Biroccio A, Ceccacci A, Pacini L, Narjes F, Gennari N, Bisbocci M, Incitti I, Orsatti L, Harper S, Stansfield I, Rowley M, De FR, Migliaccio G (2003) Mechanism of action and antiviral activity of benzimidazole-based allosteric inhibitors of the hepatitis C virus RNA-dependent RNA polymerase. J Virol 77:13225–13231

    Article  PubMed  CAS  Google Scholar 

  • Tomei L, Altamura S, Bartholomew L, Bisbocci M, Bailey C, Bosserman M, Cellucci A, Forte E, Incitti I, Orsatti L, Koch U, De FR, Olsen DB, Carroll SS, Migliaccio G (2004) Characterization of the inhibition of hepatitis C virus RNA replication by nonnucleosides. J Virol 78:938–946

    Article  PubMed  CAS  Google Scholar 

  • Tong X, Chase R, Skelton A, Chen T, Wright-Minogue J, Malcolm BA (2006) Identification and analysis of fitness of resistance mutations against the HCV protease inhibitor SCH 503034. Antiviral Res 70:28–38

    Article  PubMed  CAS  Google Scholar 

  • Warner N, Locarnini S, Kuiper M, Bartholomeusz A, Ayres A, Yuen L, Shaw T (2007) The L80I substitution in the reverse transcriptase domain of the hepatitis B virus polymerase is associated with lamivudine resistance and enhanced viral replication in vitro. Antimicrob Agents Chemother 51:2285–2292

    Article  PubMed  CAS  Google Scholar 

  • Weinstock HS, Zaidi I, Heneine W, Bennett D, Garcia-Lerma JG, Douglas JM Jr, LaLota M, Dickinson G, Schwarcz S, Torian L, Wendell D, Paul S, Goza GA, Ruiz J, Boyett B, Kaplan JE (2004) The epidemiology of antiretroviral drug resistance among drug-naive HIV-1-infected persons in 10 US cities. J Infect Dis 189:2174–2180

    Article  PubMed  Google Scholar 

  • Wensing AM, Boucher CA (2003) Worldwide transmission of drug-resistant HIV. AIDS Rev 5:140–155

    PubMed  Google Scholar 

  • Whitley RJ, Hayden FG, Reisinger KS, Young N, Dutkowski R, Ipe D, Mills RG, Ward P (2001) Oral oseltamivir treatment of influenza in children. Pediatr Infect Dis J 20:127–133

    Article  PubMed  CAS  Google Scholar 

  • Wolfs TF, Zwart G, Bakker M, Goudsmit J (1992) HIV-1 genomic RNA diversification following sexual and parenteral virus transmission. Virol 189:103–110

    Article  CAS  Google Scholar 

  • Yi M, Tong X, Skelton A, Chase R, Chen T, Prongay A, Bogen SL, Saksena AK, Njoroge FG, Veselenak RL, Pyles RB, Bourne N, Malcolm BA, Lemon SM (2006) Mutations conferring resistance to SCH6, a novel hepatitis C virus NS3/4A protease inhibitor. Reduced RNA replication fitness and partial rescue by second-site mutations. J Biol Chem 281:8205–8215

    Article  PubMed  CAS  Google Scholar 

  • Zhang Y-M, Imamichi H, Imamichi T, Lane HC, Falloon J, Vasudevachari MB, Salzman NP (1997) Drug resistance during indinavir therapy is caused by mutations in the protease gene and in its gag substrate cleavage sites. J Virol 71:6662–6670

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands

    M. Nijhuis, N.M. van Maarseveen & C.A.B. Boucher

Authors
  1. M. Nijhuis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N.M. van Maarseveen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C.A.B. Boucher
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C.A.B. Boucher .

Editor information

Editors and Affiliations

  1. Hygiene Institute Department of Virology, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 324, Heidelberg, 69120, Germany

    Hans-Georg Kräusslich  & Ralf Bartenschlager  & 

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Nijhuis, M., van Maarseveen, N., Boucher, C. (2009). Antiviral Resistance and Impact on Viral Replication Capacity: Evolution of Viruses Under Antiviral Pressure Occurs in Three Phases. In: Kräusslich, HG., Bartenschlager, R. (eds) Antiviral Strategies. Handbook of Experimental Pharmacology, vol 189. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-79086-0_11

Download citation

Publish with us

Policies and ethics

Search

Navigation