Models of Viral Population Dynamics

  • Pranesh Padmanabhan
  • Narendra M. DixitEmail author
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 392)


Models of viral population dynamics have contributed enormously to our understanding of the pathogenesis and transmission of several infectious diseases, the coevolutionary dynamics of viruses and their hosts, the mechanisms of action of drugs, and the effectiveness of interventions. In this chapter, we review major advances in the modeling of the population dynamics of the human immunodeficiency virus (HIV) and briefly discuss adaptations to other viruses.


Human Immunodeficiency Virus Human Immunodeficiency Virus Infection Human Immunodeficiency Virus Replication Viral Dynamic Human Immunodeficiency Virus Protease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was supported by the Department of Science and Technology, Government of India.


  1. Abram ME, Ferris AL, Shao W et al (2010) Nature, position, and frequency of mutations made in a single cycle of HIV-1 replication. J Virol 84:9864–9878PubMedPubMedCentralCrossRefGoogle Scholar
  2. Adiwijaya BS, Herrmann E, Hare B et al (2010) A multi-variant, viral dynamic model of genotype 1 HCV to assess the in vivo evolution of protease-inhibitor resistant variants. PLoS Comput Biol 6:e1000745PubMedPubMedCentralCrossRefGoogle Scholar
  3. Alexander HK, Bonhoeffer S (2013) Pre-existence and emergence of drug resistance in a generalized model of intra-host viral dynamics. Epidemics 4:187–202CrossRefGoogle Scholar
  4. Alizon S, Magnus C (2012) Modelling the course of an HIV infection: insights from ecology and evolution. Viruses 4:1984–2013PubMedPubMedCentralCrossRefGoogle Scholar
  5. Althaus CL, Bonhoeffer S (2005) Stochastic interplay between mutation and recombination during the acquisition of drug resistance mutations in human immunodeficiency virus type 1. J Virol 79:13572–13578PubMedPubMedCentralCrossRefGoogle Scholar
  6. Arora P, Dixit NM (2009) Timing the emergence of resistance to anti-HIV drugs with large genetic barriers. PLoS Comput Biol 5:e1000305PubMedPubMedCentralCrossRefGoogle Scholar
  7. Asquith B, Edwards CT, Lipsitch M et al (2006) Inefficient cytotoxic T lymphocyte-mediated killing of HIV-1-infected cells in vivo. PLoS Biol 4:e90PubMedPubMedCentralCrossRefGoogle Scholar
  8. Austin DJ, White NJ, Anderson RM (1998) The dynamics of drug action on the within-host population growth of infectious agents: melding pharmacokinetics with pathogen population dynamics. J Theor Biol 194:313–339PubMedCrossRefGoogle Scholar
  9. Baccam P, Beauchemin C, Macken CA et al (2006) Kinetics of influenza A virus infection in humans. J Virol 80:7590–7599PubMedPubMedCentralCrossRefGoogle Scholar
  10. Balagam R, Singh V, Sagi AR et al (2011) Taking multiple infections of cells and recombination into account leads to small within-host effective-population-size estimates of HIV-1. PLoS ONE 6:e14531PubMedPubMedCentralCrossRefGoogle Scholar
  11. Ballana E, Esté J (2012) HIV-1 infection and CCR5Δ32 homozygosis. Future Virol 7:653–658CrossRefGoogle Scholar
  12. Batorsky R, Kearney MF, Palmer SE et al (2011) Estimate of effective recombination rate and average selection coefficient for HIV in chronic infection. Proc Natl Acad Sci USA 108:5661–5666PubMedPubMedCentralCrossRefGoogle Scholar
  13. Beauchemin CA, McSharry JJ, Drusano GL et al (2008) Modeling amantadine treatment of influenza A virus in vitro. J Theor Biol 254:439–451PubMedPubMedCentralCrossRefGoogle Scholar
  14. Binder M, Sulaimanov N, Clausznitzer D et al (2013) Replication vesicles are load- and choke-points in the hepatitis C virus lifecycle. PLoS Pathog 9:e1003561PubMedPubMedCentralCrossRefGoogle Scholar
  15. Bocharov G, Ford NJ, Edwards J et al (2005) A genetic-algorithm approach to simulating human immunodeficiency virus evolution reveals the strong impact of multiply infected cells and recombination. J Gen Virol 86:3109–3118PubMedCrossRefGoogle Scholar
  16. Boerlijst MC, Bonhoeffer S, Nowak MA (1996) Viral quasi-species and recombination. Proc R Soc Lond B 263:1577–1584Google Scholar
  17. Bonhoeffer S, Nowak MA (1997) Pre-existence and emergence of drug resistance in HIV-1 infection. Proc Biol Sci 264:631–637PubMedPubMedCentralCrossRefGoogle Scholar
  18. Bonhoeffer S, May RM, Shaw GM et al (1997) Virus dynamics and drug therapy. Proc Natl Acad Sci USA 94:6971–6976PubMedPubMedCentralCrossRefGoogle Scholar
  19. Bonhoeffer S, Funk GA, Gunthard HF et al (2003) Glancing behind virus load variation in HIV-1 infection. Trends Microbiol 11:499–504PubMedCrossRefGoogle Scholar
  20. Bretscher MT, Althaus CL, Muller V et al (2004) Recombination in HIV and the evolution of drug resistance: for better or for worse? BioEssays 26:180–188PubMedCrossRefGoogle Scholar
  21. 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 94:1862–1865PubMedPubMedCentralCrossRefGoogle Scholar
  22. Carvajal-Rodriguez A, Crandall KA, Posada D (2007) Recombination favors the evolution of drug resistance in HIV-1 during antiretroviral therapy. Infect Genet Evol 7:476–483PubMedPubMedCentralCrossRefGoogle Scholar
  23. Cen S, Peng ZG, Li XY et al (2010) Small molecular compounds inhibit HIV-1 replication through specifically stabilizing APOBEC3G. J Biol Chem 285:16546–16552PubMedPubMedCentralCrossRefGoogle Scholar
  24. Chang DB, Young CS (2007) Simple scaling laws for influenza A rise time, duration, and severity. J Theor Biol 246:621–635PubMedCrossRefGoogle Scholar
  25. Chatterjee A, Smith PF, Perelson AS (2013) Hepatitis C viral kinetics: the past, present, and future. Clin Liver Dis 17:13–26PubMedPubMedCentralCrossRefGoogle Scholar
  26. Christiansen FB, Otto SP, Bergman A et al (1998) Waiting with and without recombination: the time to production of a double mutant. Theor Popul Biol 53:199–215PubMedCrossRefGoogle Scholar
  27. Chun TW, Carruth L, Finzi D et al (1997) Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection. Nature 387:183–188PubMedCrossRefGoogle Scholar
  28. Clavel F, Hance AJ (2004) HIV drug resistance. N Engl J Med 350:1023–1035PubMedCrossRefGoogle Scholar
  29. Coombs D, Gilchrist MA, Ball CL (2007) Evaluating the importance of within- and between-host selection pressures on the evolution of chronic pathogens. Theor Popul Biol 72:576–591PubMedCrossRefGoogle Scholar
  30. Dahari H, Ribeiro RM, Perelson AS (2007a) Triphasic decline of hepatitis C virus RNA during antiviral therapy. Hepatology 46:16–21PubMedCrossRefGoogle Scholar
  31. Dahari H, Ribeiro RM, Rice CM et al (2007b) Mathematical modeling of subgenomic hepatitis C virus replication in Huh-7 cells. J Virol 81:750–760PubMedPubMedCentralCrossRefGoogle Scholar
  32. Dapp MJ, Clouser CL, Patterson S et al (2009) 5-Azacytidine can induce lethal mutagenesis in human immunodeficiency virus type 1. J Virol 83:11950–11958PubMedPubMedCentralCrossRefGoogle Scholar
  33. De Boer RJ, Perelson AS (2013) Quantifying T lymphocyte turnover. J Theor Biol 327:45–87PubMedPubMedCentralCrossRefGoogle Scholar
  34. Deeks SG, Walker BD (2007) Human immunodeficiency virus controllers: mechanisms of durable virus control in the absence of antiretroviral therapy. Immunity 27:406–416PubMedCrossRefGoogle Scholar
  35. Deeks SG, Lewin SR, Havlir DV (2013) The end of AIDS: HIV infection as a chronic disease. Lancet 382:1525–1533PubMedPubMedCentralCrossRefGoogle Scholar
  36. Dixit NM, Perelson AS (2004) Complex patterns of viral load decay under antiretroviral therapy: influence of pharmacokinetics and intracellular delay. J Theor Biol 226:95–109PubMedCrossRefGoogle Scholar
  37. Dixit NM, Perelson AS (2005) Influence of drug pharmacokinetics on HIV pathogenesis and therapy. In: Wu H, Tan WY (eds) Deterministic and stochastic models on AIDS and HIV with intervention. World Scientific Press, Singapore, pp 287–311CrossRefGoogle Scholar
  38. 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
  39. Dixit NM, Srivastava P, Vishnoi NK (2012) A finite population model of molecular evolution: theory and computation. J Comput Biol 19:1176–1202PubMedCrossRefGoogle Scholar
  40. Doyon L, Tremblay S, Bourgon L et al (2005) Selection and characterization of HIV-1 showing reduced susceptibility to the non-peptidic protease inhibitor tipranavir. Antiviral Res 68:27–35PubMedCrossRefGoogle Scholar
  41. Eigen M (1971) Selforganization of matter and the evolution of biological macromolecules. Naturwissenschaften 58:465–523PubMedCrossRefGoogle Scholar
  42. Eigen M (2002) Error catastrophe and antiviral strategy. Proc Natl Acad Sci USA 99:13374–13376PubMedPubMedCentralCrossRefGoogle Scholar
  43. Eigen M, McCaskill J, Schuster P (1989) The molecular quasi-species. Adv Chem Phys 75:149–263Google Scholar
  44. Ejima T, Hirota M, Mizukami T et al (2011) An anti-HIV-1 compound that increases steady-state expression of apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G. Int J Mol Med 28:613–616PubMedGoogle Scholar
  45. Elemans M, Florins A, Willems L et al (2014) Rates of CTL killing in persistent viral infection in vivo. PLoS Comput Biol 10:e1003534PubMedPubMedCentralCrossRefGoogle Scholar
  46. Emery VC, Cope AV, Bowen EF et al (1999) The dynamics of human cytomegalovirus replication in vivo. J Exp Med 190:177–182PubMedPubMedCentralCrossRefGoogle Scholar
  47. Emery VC, Hassan-Walker AF, Burroughs AK et al (2002) Human cytomegalovirus (HCMV) replication dynamics in HCMV-naive and -experienced immunocompromised hosts. J Infect Dis 185:1723–1728PubMedCrossRefGoogle Scholar
  48. Fellay J, Ge D, Shianna KV et al (2009) Common genetic variation and the control of HIV-1 in humans. PLoS Genet 5:e1000791PubMedPubMedCentralCrossRefGoogle Scholar
  49. Fraser C (2005) HIV recombination: what is the impact on antiretroviral therapy? J R Soc Interface 2:489–503PubMedPubMedCentralCrossRefGoogle Scholar
  50. Fraser C, Hollingsworth TD, Chapman R et al (2007) Variation in HIV-1 set-point viral load: epidemiological analysis and an evolutionary hypothesis. Proc Natl Acad Sci USA 104:17441–17446PubMedPubMedCentralCrossRefGoogle Scholar
  51. Fraser C, Lythgoe K, Leventhal GE et al (2014) Virulence and pathogenesis of HIV-1 infection: an evolutionary perspective. Science 343:1243727PubMedCrossRefGoogle Scholar
  52. Gadhamsetty S, Dixit NM (2010) Estimating frequencies of minority nevirapine-resistant strains in chronically HIV-1-infected individuals naive to nevirapine by using stochastic simulations and a mathematical model. J Virol 84:10230–10240PubMedPubMedCentralCrossRefGoogle Scholar
  53. Gadhamsetty S, Maree AF, Beltman JB et al (2014) A general functional response of cytotoxic T lymphocyte-mediated killing of target cells. Biophys J 106:1780–1791PubMedPubMedCentralCrossRefGoogle Scholar
  54. Ganusov VV, De Boer RJ (2006) Estimating costs and benefits of CTL escape mutations in SIV/HIV infection. PLoS Comput Biol 2:e24PubMedPubMedCentralCrossRefGoogle Scholar
  55. Ganusov VV, Goonetilleke N, Liu MK et al (2011) Fitness costs and diversity of the cytotoxic T lymphocyte (CTL) response determine the rate of CTL escape during acute and chronic phases of HIV infection. J Virol 85:10518–10528PubMedPubMedCentralCrossRefGoogle Scholar
  56. Ghany MG, Nelson DR, Strader DB et al (2011) An update on treatment of genotype 1 chronic hepatitis C virus infection: 2011 practice guideline by the American Association for the Study of Liver Diseases. Hepatology 54:1433–1444PubMedPubMedCentralCrossRefGoogle Scholar
  57. Gheorghiu-Svirschevski S, Rouzine IM, Coffin JM (2007) Increasing sequence correlation limits the efficiency of recombination in a multisite evolution model. Mol Biol Evol 24:574–586PubMedCrossRefGoogle Scholar
  58. Gilmore JB, Kelleher AD, Cooper DA et al (2013) Explaining the determinants of first phase HIV decay dynamics through the effects of stage-dependent drug action. PLoS Comput Biol 9:e1002971PubMedPubMedCentralCrossRefGoogle Scholar
  59. Guedj J, Dahari H, Pohl RT et al (2012) Understanding silibinin’s modes of action against HCV using viral kinetic modeling. J Hepatol 56:1019–1024PubMedPubMedCentralCrossRefGoogle Scholar
  60. Guedj J, Dahari H, Rong L et al (2013) Modeling shows that the NS5A inhibitor daclatasvir has two modes of action and yields a shorter estimate of the hepatitis C virus half-life. Proc Natl Acad Sci USA 110:3991–3996PubMedPubMedCentralCrossRefGoogle Scholar
  61. Hancioglu B, Swigon D, Clermont G (2007) A dynamical model of human immune response to influenza A virus infection. J Theor Biol 246:70–86PubMedCrossRefGoogle Scholar
  62. Harris KS, Brabant W, Styrchak S et al (2005) KP-1212/1461, a nucleoside designed for the treatment of HIV by viral mutagenesis. Antiviral Res 67:1–9PubMedCrossRefGoogle Scholar
  63. Hartl DL, Clark AG (2007) Principles of Population Genetics. Sinauer Associates Inc., SunderlandGoogle Scholar
  64. Heim MH (2013a) 25 years of interferon-based treatment of chronic hepatitis C: an epoch coming to an end. Nat Rev Immunol 13:535–542PubMedCrossRefGoogle Scholar
  65. Heim MH (2013b) Innate immunity and HCV. J Hepatol 58:564–574PubMedCrossRefGoogle Scholar
  66. Heldt FS, Frensing T, Pflugmacher A et al (2013) Multiscale modeling of influenza A virus infection supports the development of direct-acting antivirals. PLoS Comput Biol 9:e1003372PubMedPubMedCentralCrossRefGoogle Scholar
  67. Herz AV, Bonhoeffer S, Anderson RM et al (1996) Viral dynamics in vivo: limitations on estimates of intracellular delay and virus decay. Proc Natl Acad Sci USA 93:7247–7251PubMedPubMedCentralCrossRefGoogle Scholar
  68. Ho DD, Neumann AU, Perelson AS et al (1995) Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature 373:123–126PubMedCrossRefGoogle Scholar
  69. Hoetelmans RM (1998) Sanctuary sites in HIV-1 infection. Antivir Ther 3(Suppl 4):13–17PubMedGoogle Scholar
  70. Holder BP, Simon P, Liao LE et al (2011) Assessing the in vitro fitness of an oseltamivir-resistant seasonal A/H1N1 influenza strain using a mathematical model. PLoS ONE 6:e14767PubMedPubMedCentralCrossRefGoogle Scholar
  71. Jefferson T, Demicheli V, Rivetti D et al (2006) Antivirals for influenza in healthy adults: systematic review. Lancet 367:303–313PubMedCrossRefGoogle Scholar
  72. Jilek BL, Zarr M, Sampah ME et al (2012) A quantitative basis for antiretroviral therapy for HIV-1 infection. Nat Med 18:446–451PubMedPubMedCentralCrossRefGoogle Scholar
  73. Johnson VA, Calvez V, Gunthard HF et al (2013) Update of the drug resistance mutations in HIV-1: March 2013. Top Antivir Med 21:6–14PubMedGoogle Scholar
  74. Josefsson L, King MS, Makitalo B et al (2011) Majority of CD4+ T cells from peripheral blood of HIV-1-infected individuals contain only one HIV DNA molecule. Proc Natl Acad Sci USA 108:11199–11204PubMedPubMedCentralCrossRefGoogle Scholar
  75. Josefsson L, Palmer S, Faria NR et al (2013) Single cell analysis of lymph node tissue from HIV-1 infected patients reveals that the majority of CD4+ T-cells contain one HIV-1 DNA molecule. PLoS Pathog 9:e1003432PubMedPubMedCentralCrossRefGoogle Scholar
  76. Jung A, Maier R, Vartanian JP et al (2002) Recombination: multiply infected spleen cells in HIV patients. Nature 418:144PubMedCrossRefGoogle Scholar
  77. Kosmrlj A, Read EL, Qi Y et al (2010) Effects of thymic selection of the T-cell repertoire on HLA class I-associated control of HIV infection. Nature 465:350–354PubMedPubMedCentralCrossRefGoogle Scholar
  78. Kouyos RD, Althaus CL, Bonhoeffer S (2006) Stochastic or deterministic: what is the effective population size of HIV-1? Trends Microbiol 14:507–511PubMedCrossRefGoogle Scholar
  79. Kouyos RD, Fouchet D, Bonhoeffer S (2009) Recombination and drug resistance in HIV: population dynamics and stochasticity. Epidemics 1:58–69PubMedCrossRefGoogle Scholar
  80. Levy DN, Aldrovandi GM, Kutsch O et al (2004) Dynamics of HIV-1 recombination in its natural target cells. Proc Natl Acad Sci USA 101:4204–4209PubMedPubMedCentralCrossRefGoogle Scholar
  81. Little SJ, McLean AR, Spina CA et al (1999) Viral dynamics of acute HIV-1 infection. J Exp Med 190:841–850PubMedPubMedCentralCrossRefGoogle Scholar
  82. Loeb LA, Essigmann JM, Kazazi F et al (1999) Lethal mutagenesis of HIV with mutagenic nucleoside analogs. Proc Natl Acad Sci USA 96:1492–1497PubMedPubMedCentralCrossRefGoogle Scholar
  83. Maldarelli F, Palmer S, King MS et al (2007) ART suppresses plasma HIV-1 RNA to a stable set point predicted by pretherapy viremia. PLoS Pathog 3:e46PubMedPubMedCentralCrossRefGoogle Scholar
  84. Malim MH (2009) APOBEC proteins and intrinsic resistance to HIV-1 infection. Philos Trans R Soc Lond B Biol Sci 364:675–687PubMedPubMedCentralCrossRefGoogle Scholar
  85. Mansky LM, Temin HM (1995) Lower in vivo mutation rate of human immunodeficiency virus type 1 than that predicted from the fidelity of purified reverse transcriptase. J Virol 69:5087–5094PubMedPubMedCentralGoogle Scholar
  86. Markowitz M, Louie M, Hurley A et al (2003) A novel antiviral intervention results in more accurate assessment of human immunodeficiency virus type 1 replication dynamics and T-cell decay in vivo. J Virol 77:5037–5038PubMedPubMedCentralCrossRefGoogle Scholar
  87. Miao H, Hollenbaugh JA, Zand MS et al (2010) Quantifying the early immune response and adaptive immune response kinetics in mice infected with influenza A virus. J Virol 84:6687–6698PubMedPubMedCentralCrossRefGoogle Scholar
  88. Mohanty U, Dixit NM (2008) Mechanism-based model of the pharmacokinetics of enfuvirtide, an HIV fusion inhibitor. J Theor Biol 251:541–551PubMedPubMedCentralCrossRefGoogle Scholar
  89. Mohri H, Bonhoeffer S, Monard S et al (1998) Rapid turnover of T lymphocytes in SIV-infected rhesus macaques. Science 279:1223–1227PubMedCrossRefGoogle Scholar
  90. Mostowy R, Kouyos RD, Fouchet D et al (2011) The role of recombination for the coevolutionary dynamics of HIV and the immune response. PLoS ONE 6:e16052PubMedPubMedCentralCrossRefGoogle Scholar
  91. 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
  92. Murillo LN, Murillo MS, Perelson AS (2013) Towards multiscale modeling of influenza infection. J Theor Biol 332:267–290PubMedPubMedCentralCrossRefGoogle Scholar
  93. Nathans R, Cao H, Sharova N et al (2008) Small-molecule inhibition of HIV-1 Vif. Nat Biotechnol 26:1187–1192PubMedPubMedCentralCrossRefGoogle Scholar
  94. Neher RA, Leitner T (2010) Recombination rate and selection strength in HIV intra-patient evolution. PLoS Comput Biol 6:e1000660PubMedPubMedCentralCrossRefGoogle Scholar
  95. 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
  96. Nijhuis M, Boucher CA, Schipper P et al (1998) Stochastic processes strongly influence HIV-1 evolution during suboptimal protease-inhibitor therapy. Proc Natl Acad Sci USA 95:14441–14446PubMedPubMedCentralCrossRefGoogle Scholar
  97. Nowak MA, May RM (2000) Virus dynamics: mathematical principles of immunology and virology. Oxford University Press, New YorkGoogle Scholar
  98. Nowak MA, McLean AR (1991) A mathematical model of vaccination against HIV to prevent the development of AIDS. Proc Biol Sci 246:141–146PubMedCrossRefGoogle Scholar
  99. Nowak M, Schuster P (1989) Error thresholds of replication in finite populations mutation frequencies and the onset of Muller’s ratchet. J Theor Biol 137:375–395PubMedCrossRefGoogle Scholar
  100. Nowak MA, May RM, Anderson RM (1990) The evolutionary dynamics of HIV-1 quasispecies and the development of immunodeficiency disease. Aids 4:1095–1103PubMedCrossRefGoogle Scholar
  101. Nowak MA, May RM, Phillips RE et al (1995) Antigenic oscillations and shifting immunodominance in HIV-1 infections. Nature 375:606–611PubMedCrossRefGoogle Scholar
  102. Nowak MA, Bonhoeffer S, Hill AM et al (1996) Viral dynamics in hepatitis B virus infection. Proc Natl Acad Sci USA 93:4398–4402PubMedPubMedCentralCrossRefGoogle Scholar
  103. Padmanabhan P, Dixit NM (2011) Mathematical model of viral kinetics in vitro estimates the number of E2-CD81 complexes necessary for hepatitis C virus entry. PLoS Comput Biol 7:e1002307PubMedPubMedCentralCrossRefGoogle Scholar
  104. Padmanabhan P, Dixit NM (2012) Viral kinetics suggests a reconciliation of the disparate observations of the modulation of Claudin-1 expression on cells exposed to hepatitis C virus. PLoS ONE 7:e36107PubMedPubMedCentralCrossRefGoogle Scholar
  105. Padmanabhan P, Garaigorta U, Dixit NM (2014) Emergent properties of the interferon signaling network may underlie the success of hepatitis C treatment. Nat Commun. doi: 10.1038/ncomms4872 Google Scholar
  106. Palmer S, Maldarelli F, Wiegand A et al (2008) Low-level viremia persists for at least 7 years in patients on suppressive antiretroviral therapy. Proc Natl Acad Sci USA 105:3879–3884PubMedPubMedCentralCrossRefGoogle Scholar
  107. Pawelek KA, Huynh GT, Quinlivan M et al (2012) Modeling within-host dynamics of influenza virus infection including immune responses. PLoS Comput Biol 8:e1002588PubMedPubMedCentralCrossRefGoogle Scholar
  108. Pawlotsky JM (2014) New hepatitis C therapies: the toolbox, strategies, and challenges. Gastroenterology. doi: 10.1053/j.gastro.2014.03.003 Google Scholar
  109. Pennings PS (2012) Standing genetic variation and the evolution of drug resistance in HIV. PLoS Comput Biol 8:e1002527PubMedPubMedCentralCrossRefGoogle Scholar
  110. Pennings PS, Kryazhimskiy S, Wakeley J (2014) Loss and recovery of genetic diversity in adapting populations of HIV. PLoS Genet 10:e1004000PubMedPubMedCentralCrossRefGoogle Scholar
  111. Perelson AS (2002) Modelling viral and immune system dynamics. Nat Rev Immunol 2:28–36PubMedCrossRefGoogle Scholar
  112. Perelson AS, Ribeiro RM (2004) Hepatitis B virus kinetics and mathematical modeling. Semin Liver Dis 24(Suppl 1):11–16PubMedCrossRefGoogle Scholar
  113. Perelson AS, Ribeiro RM (2013) Modeling the within-host dynamics of HIV infection. BMC Biol 11:96PubMedPubMedCentralCrossRefGoogle Scholar
  114. 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
  115. Perelson AS, Essunger P, Cao Y et al (1997) Decay characteristics of HIV-1-infected compartments during combination therapy. Nature 387:188–191PubMedCrossRefGoogle Scholar
  116. Phillips AN (1996) Reduction of HIV concentration during acute infection: independence from a specific immune response. Science 271:497–499PubMedCrossRefGoogle Scholar
  117. Rabi SA, Laird GM, Durand CM et al (2013) Multi-step inhibition explains HIV-1 protease inhibitor pharmacodynamics and resistance. J Clin Invest 123:3848–3860PubMedPubMedCentralCrossRefGoogle Scholar
  118. Ramratnam B, Bonhoeffer S, Binley J et al (1999) Rapid production and clearance of HIV-1 and hepatitis C virus assessed by large volume plasma apheresis. Lancet 354:1782–1785PubMedCrossRefGoogle Scholar
  119. Regoes RR, Wodarz D, Nowak MA (1998) Virus dynamics: the effect of target cell limitation and immune responses on virus evolution. J Theor Biol 191:451–462PubMedCrossRefGoogle Scholar
  120. Regoes RR, Yates A, Antia R (2007) Mathematical models of cytotoxic T-lymphocyte killing. Immunol Cell Biol 85:274–279PubMedCrossRefGoogle Scholar
  121. Ribeiro RM, Bonhoeffer S (2000) Production of resistant HIV mutants during antiretroviral therapy. Proc Natl Acad Sci USA 97:7681–7686PubMedPubMedCentralCrossRefGoogle Scholar
  122. Ribeiro RM, Bonhoeffer S, Nowak MA (1998) The frequency of resistant mutant virus before antiviral therapy. AIDS 12:461–465PubMedCrossRefGoogle Scholar
  123. Ribeiro RM, Qin L, Chavez LL et al (2010) Estimation of the initial viral growth rate and basic reproductive number during acute HIV-1 infection. J Virol 84:6096–6102PubMedPubMedCentralCrossRefGoogle Scholar
  124. Ribeiro RM, Li H, Wang S et al (2012) Quantifying the diversification of hepatitis C virus (HCV) during primary infection: estimates of the in vivo mutation rate. PLoS Pathog 8:e1002881PubMedPubMedCentralCrossRefGoogle Scholar
  125. Rodrigo AG, Shpaer EG, Delwart EL et al (1999) Coalescent estimates of HIV-1 generation time in vivo. Proc Natl Acad Sci USA 96:2187–2191PubMedPubMedCentralCrossRefGoogle Scholar
  126. Rong L, Dahari H, Ribeiro RM et al (2010) Rapid emergence of protease inhibitor resistance in hepatitis C virus. Sci Transl Med 2:30ra32Google Scholar
  127. Rong L, Ribeiro RM, Perelson AS (2012) Modeling quasispecies and drug resistance in hepatitis C patients treated with a protease inhibitor. Bull Math Biol 74:1789–1817PubMedPubMedCentralCrossRefGoogle Scholar
  128. Rosenbloom DI, Hill AL, Rabi SA et al (2013) Antiretroviral dynamics determines HIV evolution and predicts therapy outcome. Nat Med 18:1378–1385CrossRefGoogle Scholar
  129. Rouzine IM, Coffin JM (1999) Linkage disequilibrium test implies a large effective population number for HIV in vivo. Proc Natl Acad Sci USA 96:10758–10763PubMedPubMedCentralCrossRefGoogle Scholar
  130. Rouzine IM, Coffin JM (2005) Evolution of human immunodeficiency virus under selection and weak recombination. Genetics 170:7–18PubMedPubMedCentralCrossRefGoogle Scholar
  131. Saakian DB, Hu CK (2006) Exact solution of the Eigen model with general fitness functions and degradation rates. Proc Natl Acad Sci USA 103:4935–4939PubMedPubMedCentralCrossRefGoogle Scholar
  132. Saenz RA, Quinlivan M, Elton D et al (2010) Dynamics of influenza virus infection and pathology. J Virol 84:3974–3983PubMedPubMedCentralCrossRefGoogle Scholar
  133. Sampah ME, Shen L, Jilek BL et al (2011) Dose-response curve slope is a missing dimension in the analysis of HIV-1 drug resistance. Proc Natl Acad Sci USA 108:7613–7618PubMedPubMedCentralCrossRefGoogle Scholar
  134. Schlub TE, Grimm AJ, Smyth RP et al (2014) Fifteen to twenty percent of HIV substitution mutations are associated with recombination. J Virol 88:3837–3849PubMedPubMedCentralCrossRefGoogle Scholar
  135. Sedaghat AR, Dinoso JB, Shen L et al (2008) Decay dynamics of HIV-1 depend on the inhibited stages of the viral life cycle. Proc Natl Acad Sci USA 105:4832–4837PubMedPubMedCentralCrossRefGoogle Scholar
  136. Seo TK, Thorne JL, Hasegawa M et al (2002) Estimation of effective population size of HIV-1 within a host: a pseudomaximum-likelihood approach. Genetics 160:1283–1293PubMedPubMedCentralGoogle Scholar
  137. Shen L, Peterson S, Sedaghat AR et al (2008) Dose-response curve slope sets class-specific limits on inhibitory potential of anti-HIV drugs. Nat Med 14:762–766PubMedPubMedCentralCrossRefGoogle Scholar
  138. Shen L, Rabi SA, Sedaghat AR et al. (2011) A critical subset model provides a conceptual basis for the high antiviral activity of major HIV drugs. Sci Transl Med 3:91ra63Google Scholar
  139. Siliciano RF, Greene WC (2011) HIV latency. Cold Spring Harb Perspect Med 1:a007096PubMedPubMedCentralCrossRefGoogle Scholar
  140. Simek MD, Rida W, Priddy FH et al (2009) Human immunodeficiency virus type 1 elite neutralizers: individuals with broad and potent neutralizing activity identified by using a high-throughput neutralization assay together with an analytical selection algorithm. J Virol 83:7337–7348PubMedPubMedCentralCrossRefGoogle Scholar
  141. Smith RJ (2006) Adherence to antiretroviral HIV drugs: how many doses can you miss before resistance emerges? Proc Biol Sci 273:617–624PubMedPubMedCentralCrossRefGoogle Scholar
  142. Smith HC (2011) APOBEC3G: a double agent in defense. Trends Biochem Sci 36:239–244PubMedPubMedCentralCrossRefGoogle Scholar
  143. Smith AM, Adler FR, McAuley JL et al (2011) Effect of 1918 PB1-F2 expression on influenza A virus infection kinetics. PLoS Comput Biol 7:e1001081PubMedPubMedCentralCrossRefGoogle Scholar
  144. Stafford MA, Corey L, Cao Y et al (2000) Modeling plasma virus concentration during primary HIV infection. J Theor Biol 203:285–301PubMedCrossRefGoogle Scholar
  145. Stephenson KE, Barouch DH (2013) A global approach to HIV-1 vaccine development. Immunol Rev 254:295–304PubMedPubMedCentralCrossRefGoogle Scholar
  146. Summers J, Litwin S (2006) Examining the theory of error catastrophe. J Virol 80:20–26PubMedPubMedCentralCrossRefGoogle Scholar
  147. Suryavanshi GW, Dixit NM (2007) Emergence of recombinant forms of HIV: dynamics and scaling. PLoS Comput Biol 3:2003–2018PubMedCrossRefGoogle Scholar
  148. Taubenberger JK, Morens DM (2008) The pathology of influenza virus infections. Annu Rev Pathol 3:499–522PubMedPubMedCentralCrossRefGoogle Scholar
  149. Tebas P, Stein D, Tang WW et al (2014) Gene editing of CCR5 in autologous CD4 T cells of persons infected with HIV. N Engl J Med 370:901–910PubMedPubMedCentralCrossRefGoogle Scholar
  150. Thangavelu PU, Gupta V, Dixit NM (2014) Estimating the fraction of progeny virions that must incorporate APOBEC3G for suppression of productive HIV-1 infection. Virology 449:224–228PubMedCrossRefGoogle Scholar
  151. Thomas E, Ghany MG, Liang TJ (2012) The application and mechanism of action of ribavirin in therapy of hepatitis C. Antivir Chem Chemother 23:1–12PubMedCrossRefGoogle Scholar
  152. Tripathi K, Balagam R, Vishnoi NK et al (2012) Stochastic simulations suggest that HIV-1 survives close to its error threshold. PLoS Comput Biol 8:e1002684PubMedPubMedCentralCrossRefGoogle Scholar
  153. Vaidya NK, Ribeiro RM, Miller CJ et al (2010) Viral dynamics during primary simian immunodeficiency virus infection: effect of time-dependent virus infectivity. J Virol 84:4302–4310PubMedPubMedCentralCrossRefGoogle Scholar
  154. Vijay NN, Vasantika Ajmani R et al (2008) Recombination increases human immunodeficiency virus fitness, but not necessarily diversity. J Gen Virol 89:1467–1477PubMedCrossRefGoogle Scholar
  155. Volberding PA, Deeks SG (2010) Antiretroviral therapy and management of HIV infection. Lancet 376:49–62PubMedCrossRefGoogle Scholar
  156. Wahl LM, Nowak MA (2000) Adherence and drug resistance: predictions for therapy outcome. Proc Biol Sci 267:835–843PubMedPubMedCentralCrossRefGoogle Scholar
  157. Wei X, Ghosh SK, Taylor ME et al (1995) Viral dynamics in human immunodeficiency virus type 1 infection. Nature 373:117–122PubMedCrossRefGoogle Scholar
  158. Weiss JN (1997) The Hill equation revisited: uses and misuses. Faseb J 11:835–841PubMedGoogle Scholar
  159. Wilke CO (2005) Quasispecies theory in the context of population genetics. BMC Evol Biol 5:44PubMedPubMedCentralCrossRefGoogle Scholar
  160. Wu H, Huang Y, Acosta EP et al (2005) Modeling long-term HIV dynamics and antiretroviral response: effects of drug potency, pharmacokinetics, adherence, and drug resistance. J Acquir Immune Defic Syndr 39:272–283PubMedCrossRefGoogle Scholar
  161. Yates A, Graw F, Barber DL et al (2007) Revisiting estimates of CTL killing rates in vivo. PLoS ONE 2:e1301PubMedPubMedCentralCrossRefGoogle Scholar
  162. Zhang J, Lipton HL, Perelson AS et al (2013) Modeling the acute and chronic phases of Theiler murine encephalomyelitis virus infection. J Virol 87:4052–4059PubMedPubMedCentralCrossRefGoogle Scholar

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© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Department of Chemical EngineeringIndian Institute of ScienceBangaloreIndia

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