Viral quasispecies

English version

Autoři: Esteban Domingo ^aff001; Celia Perales ^aff001
Působiště autorů: Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Consejo Superior de Investigaciones Científicas (CSIC), Campus de Cantoblanco, Madrid, Spain ^aff001; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, Madrid, Spain ^aff002; Department of Clinical Microbiology, IIS-Fundación Jiménez Díaz, UAM, Madrid, Spain ^aff003
Vyšlo v časopise: Viral quasispecies. PLoS Genet 15(10): e1008271. doi:10.1371/journal.pgen.1008271
Kategorie: Topic Page
doi: https://doi.org/10.1371/journal.pgen.1008271

Souhrn

Viral quasispecies refers to a population structure that consists of extremely large numbers of variant genomes, termed mutant spectra, mutant swarms or mutant clouds. Fueled by high mutation rates, mutants arise continually, and they change in relative frequency as viral replication proceeds. The term quasispecies was adopted from a theory of the origin of life in which primitive replicons) consisted of mutant distributions, as found experimentally with present day RNA viruses. The theory provided a new definition of wild type, and a conceptual framework for the interpretation of the adaptive potential of RNA viruses that contrasted with classical studies based on consensus sequences. Standard clonal analyses and deep sequencing methodologies have confirmed the presence of myriads of mutant genomes in viral populations, and their participation in adaptive processes. The quasispecies concept applies to any biological entity, but its impact is more evident when the genome size is limited and the mutation rate is high. This is the case of the RNA viruses, ubiquitous in our biosphere, and that comprise many important pathogens. In virology, quasispecies are defined as complex distributions of closely related variant genomes subjected to genetic variation, competition and selection, and that may act as a unit of selection. Despite being an integral part of their replication, high mutation rates have an upper limit compatible with inheritable information. Crossing such a limit leads to RNA virus extinction, a transition that is the basis of an antiviral design termed lethal mutagenesis.

Klíčová slova:

Evolutionary immunology – Mammalian genomics – Microbial mutation – Mutagenesis – RNA viruses – Viral evolution – Viral genomics – Viral replication

Zdroje

1. Eigen M (1971) Self-organization of matter and the evolution of biological macromolecules. Naturwissenschaften 58: 465–523. doi: 10.1007/bf00623322 4942363

2. Eigen M, Schuster P (1979) The hypercycle. A principle of natural self-organization. Berlin: Springer.

3. Swetina J, Schuster P (1982) Self-replication with errors. A model for polynucleotide replication. Biophys Chem 16: 329–345. doi: 10.1016/0301-4622(82)87037-3 7159681

4. Fornes J, Tomas Lazaro J, Alarcon T, Elena SF, Sardanyes J (2019) Viral replication modes in single-peak fitness landscapes: A dynamical systems analysis. J Theor Biol 460: 170–183. doi: 10.1016/j.jtbi.2018.10.007 30300648

5. Schuster P (2016) Quasispecies on fitness landscapes. In: Domingo E. and Schuster P., eds. Quasispecies: From Theory to Experimental Systems. Curr Top Microbiol Immunol 392: 61–120. doi: 10.1007/82_2015_469 26597856

6. Domingo E, Sabo D, Taniguchi T, Weissmann C (1978) Nucleotide sequence heterogeneity of an RNA phage population. Cell 13: 735–744. doi: 10.1016/0092-8674(78)90223-4 657273

7. Duarte EA, Novella IS, Ledesma S, Clarke DK, Moya A, Elena SF, et al. (1994) Subclonal components of consensus fitness in an RNA virus clone. J Virol 68: 4295–4301. 8207804

8. Domingo E, Brun A, Núñez JI, Cristina J, Briones C, Escarmís C (2006) Genomics of Viruses. In: Hacker J, Dobrindt U, editors. Pathogenomics: Genome Analysis of Pathogenic Microbes. Weinheim: Wiley-VCH Verlag GmbH & Co. KGaA. pp. 369–388.

9. Batschelet E, Domingo E, Weissmann C (1976) The proportion of revertant and mutant phage in a growing population, as a function of mutation and growth rate. Gene 1: 27–32. doi: 10.1016/0378-1119(76)90004-4 1052321

10. Drake JW, Holland JJ (1999) Mutation rates among RNA viruses. Proc Natl Acad Sci USA 96: 13910–13913. doi: 10.1073/pnas.96.24.13910 10570172

11. Bradwell K, Combe M, Domingo-Calap P, Sanjuan R (2013) Correlation between mutation rate and genome size in riboviruses: mutation rate of bacteriophage Qbeta. Genetics 195: 243–251. doi: 10.1534/genetics.113.154963 23852383

12. Holland JJ, Spindler K, Horodyski F, Grabau E, Nichol S, VandePol S (1982) Rapid evolution of RNA genomes. Science 215: 1577–1585. doi: 10.1126/science.7041255 7041255

13. Domingo E, Martínez-Salas E, Sobrino F, de la Torre JC, Portela A, Ortín J, et al. (1985) The quasispecies (extremely heterogeneous) nature of viral RNA genome populations: biological relevance—a review. Gene 40: 1–8.

14. Domingo E, Holland JJ, Ahlquist P (1988) RNA Genetics. Boca Raton: CRC Press.

15. Holland J (2006) Transitions in understanding of RNA viruses: an historical perspective. Curr Top Microbiol Immunol 299: 371–401. doi: 10.1007/3-540-26397-7_14 16568907

16. Domingo E, Sheldon J, Perales C (2012) Viral quasispecies evolution. Microbiol Mol Biol Rev 76: 159–216. doi: 10.1128/MMBR.05023-11 22688811

17. Meyerhans A, Cheynier R, Albert J, Seth M, Kwok S, Sninsky J, et al. (1989) Temporal fluctuations in HIV quasispecies in vivo are not reflected by sequential HIV isolations. Cell 58: 901–910. doi: 10.1016/0092-8674(89)90942-2 2550139

18. Farci P (2011) New insights into the HCV quasispecies and compartmentalization. Semin Liver Dis 31: 356–374. doi: 10.1055/s-0031-1297925 22189976

19. Saakian DB, Hu CK (2016) Mathematical Models of Quasi-Species Theory and Exact Results for the Dynamics. Curr Top Microbiol Immunol 392: 121–139. doi: 10.1007/82_2015_471 26342705

20. Domingo E, Schuster P (2016) Quasispecies: from theory to experimental systems. Current Topics in Microbiology and Immunology. Vol. 392. Springer.

21. Steinhauer DA, Domingo E, Holland JJ (1992) Lack of evidence for proofreading mechanisms associated with an RNA virus polymerase. Gene 122: 281–288. doi: 10.1016/0378-1119(92)90216-c 1336756

22. Bernad A, Blanco L, Lazaro JM, Martin G, Salas M (1989) A conserved 3'5' exonuclease active site in prokaryotic and eukaryotic DNA polymerases. Cell 59: 219–228. doi: 10.1016/0092-8674(89)90883-0 2790959

23. Eckerle LD, Lu X, Sperry SM, Choi L, Denison MR (2007) High fidelity of murine hepatitis virus replication is decreased in nsp14 exoribonuclease mutants. J Virol 81: 12135–12144. doi: 10.1128/JVI.01296-07 17804504

24. Nagy PD, Carpenter CD, Simon AE (1997) A novel 3'-end repair mechanism in an RNA virus. Proc Natl Acad Sci U S A 94: 1113–1118. doi: 10.1073/pnas.94.4.1113 9037015

25. Bakhanashvili M (2001) Exonucleolytic proofreading by p53 protein. Eur J Biochem 268: 2047–2054. doi: 10.1046/j.1432-1327.2001.02075.x 11277927

26. Smith EC, Denison MR (2013) Coronaviruses as DNA wannabes: a new model for the regulation of RNA virus replication fidelity. PLoS Pathog 9: e1003760. doi: 10.1371/journal.ppat.1003760 24348241

27. Smith EC, Sexton NR, Denison MR (2014) Thinking Outside the Triangle: Replication Fidelity of the Largest RNA Viruses. Annu Rev Virol 1: 111–132. doi: 10.1146/annurev-virology-031413-085507 26958717

28. Wagner N, Atsmon-Raz Y, Ashkenasy G (2016) Theoretical Models of Generalized Quasispecies. Curr Top Microbiol Immunol 392: 141–159. doi: 10.1007/82_2015_456 26373410

29. Schmidt TT, Reyes G, Gries K, Ceylan CU, Sharma S, Meurer M, et al. (2017) Alterations in cellular metabolism triggered by URA7 or GLN3 inactivation cause imbalanced dNTP pools and increased mutagenesis. Proc Natl Acad Sci U S A 114: E4442–E4451. doi: 10.1073/pnas.1618714114 28416670

30. Takahashi K, Sekizuka T, Fukumoto H, Nakamichi K, Suzuki T, Sato Y, et al. (2017) Deep-Sequence Identification and Role in Virus Replication of a JC Virus Quasispecies in Patients with Progressive Multifocal Leukoencephalopathy. J Virol 91.

31. Domingo-Calap P, Schubert B, Joly M, Solis M, Untrau M, Carapito R, et al. (2018) An unusually high substitution rate in transplant-associated BK polyomavirus in vivo is further concentrated in HLA-C-bound viral peptides. PLoS Pathog 14: e1007368. doi: 10.1371/journal.ppat.1007368 30335851

32. Sanchez-Campos S, Dominguez-Huerta G, Diaz-Martinez L, Tomas DM, Navas-Castillo J, Moriones E, et al. (2018) Differential Shape of Geminivirus Mutant Spectra Across Cultivated and Wild Hosts With Invariant Viral Consensus Sequences. Front Plant Sci 9: 932. doi: 10.3389/fpls.2018.00932 30013589

33. Agol VI, Gmyl AP (2018) Emergency Services of Viral RNAs: Repair and Remodeling. Microbiol Mol Biol Rev 82. pii: e00067–17. doi: 10.1128/MMBR.00067-17 29540453

34. Figlerowicz M, Alejska M, Kurzynska-Kokorniak A, Figlerowicz M (2003) Genetic variability: the key problem in the prevention and therapy of RNA-based virus infections. Medicinal Res Reviews 23: 488–518.

35. Domingo E, Perales C (2018) Quasispecies and virus. Eur Biophys J 47: 443–457. doi: 10.1007/s00249-018-1282-6 29397419

36. Sanjuan R, Domingo-Calap P (2016) Mechanisms of viral mutation. Cell Mol Life Sci 73: 4433–4448. doi: 10.1007/s00018-016-2299-6 27392606

37. Lauring AS, Andino R (2010) Quasispecies theory and the behavior of RNA viruses. PLoS Pathog 6: e1001005. doi: 10.1371/journal.ppat.1001005 20661479

38. van Boheemen S, Tas A, Anvar SY, van Grootveld R, Albulescu IC, Bauer MP, et al. (2017) Quasispecies composition and evolution of a typical Zika virus clinical isolate from Suriname. Sci Rep 7: 2368. doi: 10.1038/s41598-017-02652-w 28539654

39. Vlok M, Lang AS, Suttle CA (2019) Marine RNA Virus Quasispecies Are Distributed throughout the Oceans. mSphere 4. pii: e00157–19. doi: 10.1128/mSphereDirect.00157-19 30944212

40. Hirose Y, Onuki M, Tenjimbayashi Y, Mori S, Ishii Y, Takeuchi T, et al. (2018) Within-Host Variations of Human Papillomavirus Reveal APOBEC Signature Mutagenesis in the Viral Genome. J Virol 92. pii: e00017–18. doi: 10.1128/JVI.00017-18 29593040

41. Gisder S, Mockel N, Eisenhardt D, Genersch E (2018) In vivo evolution of viral virulence: switching of deformed wing virus between hosts results in virulence changes and sequence shifts. Environ Microbiol 20: 4612–4628. doi: 10.1111/1462-2920.14481 30452113

42. Baccam P, Thompson RJ, Fedrigo O, Carpenter S, Cornette JL (2001) PAQ: Partition Analysis of Quasispecies. Bioinformatics 17: 16–22. doi: 10.1093/bioinformatics/17.1.16 11222259

43. Skums P, Zelikovsky A, Singh R, Gussler W, Dimitrova Z, Knyazev S, et al. (2018) QUENTIN: reconstruction of disease transmissions from viral quasispecies genomic data. Bioinformatics 34: 163–170. doi: 10.1093/bioinformatics/btx402 29304222

44. Lowry K, Woodman A, Cook J, Evans DJ (2014) Recombination in enteroviruses is a biphasic replicative process involving the generation of greater-than genome length 'imprecise' intermediates. PLoS Pathog 10: e1004191. doi: 10.1371/journal.ppat.1004191 24945141

45. Xiao Y, Rouzine IM, Bianco S, Acevedo A, Goldstein EF, Farkov M, et al. (2017) RNA Recombination Enhances Adaptability and Is Required for Virus Spread and Virulence. Cell Host Microbe 22: 420. doi: 10.1016/j.chom.2017.08.006 28910639

46. Tibayrenc M, Ayala FJ (2012) Reproductive clonality of pathogens: a perspective on pathogenic viruses, bacteria, fungi, and parasitic protozoa. Proc Natl Acad Sci U S A 109: E3305–3313. doi: 10.1073/pnas.1212452109 22949662

47. Perales C, Moreno E, Domingo E (2015) Clonality and intracellular polyploidy in virus evolution and pathogenesis. Proc Natl Acad Sci U S A 112: 8887–8892. doi: 10.1073/pnas.1501715112 26195777

48. Villarreal LP, Witzany G (2013) Rethinking quasispecies theory: From fittest type to cooperative consortia. World J Biol Chem 4: 79–90. doi: 10.4331/wjbc.v4.i4.79 24340131

49. Domingo E (2020) Virus as Populations, 2nd ed. Academic Press, Elsevier, Amsterdam.

50. Acevedo A, Brodsky L, Andino R (2014) Mutational and fitness landscapes of an RNA virus revealed through population sequencing. Nature 505: 686–690. doi: 10.1038/nature12861 24284629

51. Moreno E, Gallego I, Gregori J, Lucia-Sanz A, Soria ME, Castro V, et al. (2017) Internal Disequilibria and Phenotypic Diversification during Replication of Hepatitis C Virus in a Noncoevolving Cellular Environment. J Virol 91:e02505–16. doi: 10.1128/JVI.02505-16 28275194

52. Braun T, Borderia AV, Barbezange C, Vignuzzi M, Louzon Y (2019) Long-term context dependent genetic adaptation of the viral genetic cloud. Bioinformatics. 35:1907–1915. doi: 10.1093/bioinformatics/bty891 30346482

53. Ojosnegros S, Beerenwinkel N, Antal T, Nowak MA, Escarmis C, Domingo E (2010) Competition-colonization dynamics in an RNA virus. Proc Natl Acad Sci U S A 107: 2108–2112. doi: 10.1073/pnas.0909787107 20080701

54. Gallego I, Gregori J, Soria ME, Garcia-Crespo C, Garcia-Alvarez M, Gomez-Gonzalez A, et al. (2018) Resistance of high fitness hepatitis C virus to lethal mutagenesis. Virology 523: 100–109. doi: 10.1016/j.virol.2018.07.030 30107298

55. Holland JJ, de La Torre JC, Steinhauer DA (1992) RNA virus populations as quasispecies. Curr Top Microbiol Immunol 176: 1–20.

56. García-Arriaza J, Ojosnegros S, Dávila M, Domingo E, Escarmis C (2006) Dynamics of mutation and recombination in a replicating population of complementing, defective viral genomes. J Mol Biol 360: 558–572. doi: 10.1016/j.jmb.2006.05.027 16797586

57. Briones C, Domingo E (2008) Minority report: hidden memory genomes in HIV-1 quasispecies and possible clinical implications. AIDS Rev 10: 93–109. 18615120

58. Chumakov KM, Powers LB, Noonan KE, Roninson IB, Levenbook IS (1991) Correlation between amount of virus with altered nucleotide sequence and the monkey test for acceptability of oral poliovirus vaccine. Proc Natl Acad Sci USA 88: 199–203. doi: 10.1073/pnas.88.1.199 1846038

59. Holland JJ, editor (1992) Genetic diversity of RNA viruses. Current Topics in Microbiology and Immunology. Berlin: Springer-Verlag.

60. Perales C (2018) Quasispecies dynamics and clinical significance of hepatitis C virus (HCV) antiviral resistance. Int J Antimicrob Agents. doi: 10.1016/j.ijantimicag.2018.10.005 30315919

61. Donohue RC, Pfaller CK, Cattaneo R (2019) Cyclical adaptation of measles virus quasispecies to epithelial and lymphocytic cells: To V, or not to V. PLoS Pathog 15: e1007605. doi: 10.1371/journal.ppat.1007605 30768648

62. Martin V, Domingo E (2008) Influence of the mutant spectrum in viral evolution: focused selection of antigenic variants in a reconstructed viral quasispecies. Mol Biol Evol 25: 1544–1554. doi: 10.1093/molbev/msn099 18436553

63. Ruiz-Jarabo CM, Arias A, Baranowski E, Escarmís C, Domingo E (2000) Memory in viral quasispecies. J Virol 74: 3543–3547. doi: 10.1128/jvi.74.8.3543-3547.2000 10729128

64. Farber DL, Netea MG, Radbruch A, Rajewsky K, Zinkernagel RM (2016) Immunological memory: lessons from the past and a look to the future. Nat Rev Immunol 16: 124–128. doi: 10.1038/nri.2016.13 26831526

65. Briones C, Domingo E, Molina-París C (2003) Memory in retroviral quasispecies: experimental evidence and theoretical model for human immunodeficiency virus. J Mol Biol 331: 213–229. doi: 10.1016/s0022-2836(03)00661-2 12875847

66. Arias A, Ruiz-Jarabo CM, Escarmis C, Domingo E (2004) Fitness increase of memory genomes in a viral quasispecies. J Mol Biol 339: 405–412. doi: 10.1016/j.jmb.2004.03.061 15136042

67. Eigen M, Biebricher CK (1988) Sequence space and quasispecies distribution. In: Domingo E, Ahlquist P, Holland JJ, editors. RNA Genetics: Boca Raton, FL. CRC Press. pp. 211–245.

68. de la Torre JC, Holland JJ (1990) RNA virus quasispecies populations can suppress vastly superior mutant progeny. J Virol 64: 6278–6281. 2173792

69. Borrego B, Novella IS, Giralt E, Andreu D, Domingo E (1993) Distinct repertoire of antigenic variants of foot-and-mouth disease virus in the presence or absence of immune selection. J Virol 67: 6071–6079. 7690417

70. 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: 113–119. doi: 10.1006/viro.1996.0460 8806545

71. González-López C, Arias A, Pariente N, Gómez-Mariano G, Domingo E (2004) Preextinction viral RNA can interfere with infectivity. J Virol 78: 3319–3324. doi: 10.1128/JVI.78.7.3319-3324.2004 15016853

72. Perales C, Mateo R, Mateu MG, Domingo E (2007) Insights into RNA virus mutant spectrum and lethal mutagenesis events: replicative interference and complementation by multiple point mutants. J Mol Biol 369: 985–1000. doi: 10.1016/j.jmb.2007.03.074 17481660

73. Crowder S, Kirkegaard K (2005) Trans-dominant inhibition of RNA viral replication can slow growth of drug-resistant viruses. Nat Genet 37: 701–709. doi: 10.1038/ng1583 15965477

74. Kirkegaard K, van Buuren NJ, Mateo R (2016) My Cousin, My Enemy: quasispecies suppression of drug resistance. Curr Opin Virol 20: 106–111. doi: 10.1016/j.coviro.2016.09.011 27764731

75. Wilke CO, Wang JL, Ofria C, Lenski RE, Adami C (2001) Evolution of digital organisms at high mutation rates leads to survival of the flattest. Nature 412: 331–333. doi: 10.1038/35085569 11460163

76. Quer J, Hershey CL, Domingo E, Holland JJ, Novella IS (2001) Contingent neutrality in competing viral populations. J Virol 75: 7315–7320. doi: 10.1128/JVI.75.16.7315-7320.2001 11462003

77. Codoner FM, Daros JA, Sole RV, Elena SF (2006) The fittest versus the flattest: experimental confirmation of the quasispecies effect with subviral pathogens. PLoS Pathog 2: e136. doi: 10.1371/journal.ppat.0020136 17196038

78. Tejero H, Montero F, Nuno JC (2016) Theories of Lethal Mutagenesis: From Error Catastrophe to Lethal Defection. Curr Top Microbiol Immunol 392: 161–179. doi: 10.1007/82_2015_463 26210988

79. Pfeiffer JK, Kirkegaard K (2005) Increased fidelity reduces poliovirus fitness under selective pressure in mice. PLoS Pathogens 1: 102–110.

80. Vignuzzi M, Stone JK, Arnold JJ, Cameron CE, Andino R (2006) Quasispecies diversity determines pathogenesis through cooperative interactions in a viral population. Nature 439: 344–348. doi: 10.1038/nature04388 16327776

81. Borderia AV, Rozen-Gagnon K, Vignuzzi M (2016) Fidelity Variants and RNA Quasispecies. Curr Top Microbiol Immunol 392: 303–322. doi: 10.1007/82_2015_483 26499340

82. García-Arriaza J, Manrubia SC, Toja M, Domingo E, Escarmís C (2004) Evolutionary transition toward defective RNAs that are infectious by complementation. J Virol 78: 11678–11685. doi: 10.1128/JVI.78.21.11678-11685.2004 15479809

83. Moreno E, Ojosnegros S, Garcia-Arriaza J, Escarmis C, Domingo E, Perales C (2014) Exploration of sequence space as the basis of viral RNA genome segmentation. Proc Natl Acad Sci U S A 111: 6678–6683. doi: 10.1073/pnas.1323136111 24757055

84. Aaskov J, Buzacott K, Thu HM, Lowry K, Holmes EC (2006) Long-term transmission of defective RNA viruses in humans and Aedes mosquitoes. Science 311: 236–238. doi: 10.1126/science.1115030 16410525

85. Ciota AT, Ehrbar DJ, Van Slyke GA, Willsey GG, Kramer LD (2012) Cooperative interactions in the West Nile virus mutant swarm. BMC Evol Biol 12: 58. doi: 10.1186/1471-2148-12-58 22541042

86. Xue KS, Hooper KA, Ollodart AR, Dingens AS, Bloom JD (2016) Cooperation between distinct viral variants promotes growth of H3N2 influenza in cell culture. Elife 5: e13974. doi: 10.7554/eLife.13974 26978794

87. Shirogane Y, Watanabe S, Yanagi Y (2016) Cooperative Interaction Within RNA Virus Mutant Spectra. Curr Top Microbiol Immunol 392: 219–229. doi: 10.1007/82_2015_461 26162566

88. Pfeiffer JK, Kirkegaard K (2006) Bottleneck-mediated quasispecies restriction during spread of an RNA virus from inoculation site to brain. Proc Natl Acad Sci USA 103: 5520–5525. doi: 10.1073/pnas.0600834103 16567621

89. Gutierrez S, Michalakis Y, Blanc S (2012) Virus population bottlenecks during within-host progression and host-to-host transmission. Curr Opin Virol 2: 546–555. doi: 10.1016/j.coviro.2012.08.001 22921636

90. Bull RA, Luciani F, McElroy K, Gaudieri S, Pham ST, Chopra A, et al. (2011) Sequential bottlenecks drive viral evolution in early acute hepatitis C virus infection. PLoS Pathog 7: e1002243. doi: 10.1371/journal.ppat.1002243 21912520

91. Chao L (1990) Fitness of RNA virus decreased by Muller's ratchet. Nature 348: 454–455. doi: 10.1038/348454a0 2247152

92. Duarte E, Clarke D, Moya A, Domingo E, Holland J (1992) Rapid fitness losses in mammalian RNA virus clones due to Muller's ratchet. Proc Natl Acad Sci USA 89: 6015–6019. doi: 10.1073/pnas.89.13.6015 1321432

93. Muller HJ (1964) The relation of recombination to mutational advance. Mut Res 1: 2–9.

94. Escarmís C, Dávila M, Charpentier N, Bracho A, Moya A, Domingo E (1996) Genetic lesions associated with Muller's ratchet in an RNA virus. J Mol Biol 264: 255–267. doi: 10.1006/jmbi.1996.0639 8951375

95. Escarmís C, Dávila M, Domingo E (1999) Multiple molecular pathways for fitness recovery of an RNA virus debilitated by operation of Muller's ratchet. J Mol Biol 285: 495–505. doi: 10.1006/jmbi.1998.2366 9878424

96. Ruiz-Jarabo CM, Pariente N, Baranowski E, Dávila M, Gómez-Mariano G, Domingo E (2004) Expansion of host-cell tropism of foot-and-mouth disease virus despite replication in a constant environment. J Gen Virol 85: 2289–2297. doi: 10.1099/vir.0.80126-0 15269370

97. Martínez MA, Dopazo J, Hernandez J, Mateu MG, Sobrino F, Domingo E, et al. (1992) Evolution of the capsid protein genes of foot-and-mouth disease virus: antigenic variation without accumulation of amino acid substitutions over six decades. J Virol 66: 3557–3565. 1316467

98. Ho SY, Duchene S, Molak M, Shapiro B (2015) Time-dependent estimates of molecular evolutionary rates: evidence and causes. Mol Ecol 24: 6007–6012. doi: 10.1111/mec.13450 26769402

99. Domingo E (1989) RNA virus evolution and the control of viral disease. Progress in Drug Research 33: 93–133. 2687948

100. Williams PD (2009) Darwinian interventions: taming pathogens through evolutionary ecology. Trends Parasitol 26: 83–92. doi: 10.1016/j.pt.2009.11.009 20036799

101. Perales C, Ortega-Prieto AM, Beach NM, Sheldon J, Menendez-Arias L, Domingo E (2017) Quasispecies and drug resistance. Handbook of Antimicrobial Resistance: Springer Science+Business Media New York 2017.

102. Loeb LA, Essigmann JM, Kazazi F, Zhang J, Rose KD, Mullins JI (1999) Lethal mutagenesis of HIV with mutagenic nucleoside analogs. Proc Natl Acad Sci USA 96: 1492–1497. doi: 10.1073/pnas.96.4.1492 9990051

103. Perales C, Gallego I, De Avila AI, Soria ME, Gregori J, Quer J, et al. (2019) The increasing impact of lethal mutagenesis of viruses. Future Med. Chem. 11(13): 1645–1657. doi: 10.4155/fmc-2018-0457 31469331

104. Eigen M (2002) Error catastrophe and antiviral strategy. Proc Natl Acad Sci USA 99: 13374–13376. doi: 10.1073/pnas.212514799 12370416

105. Venkatesan S, Rosenthal R, Kanu N, McGranahan N, Bartek J, Quezada SA, et al. (2018) Perspective: APOBEC mutagenesis in drug resistance and immune escape in HIV and cancer evolution. Ann Oncol 29: 563–572. doi: 10.1093/annonc/mdy003 29324969

106. Fox EJ, Loeb LA (2010) Lethal mutagenesis: targeting the mutator phenotype in cancer. Semin Cancer Biol 20: 353–359. doi: 10.1016/j.semcancer.2010.10.005 20934515

107. Loeb LA (2011) Human cancers express mutator phenotypes: origin, consequences and targeting. Nat Rev Cancer 11: 450–457. doi: 10.1038/nrc3063 21593786

108. Page KM, Nowak MA (2002) Unifying evolutionary dynamics. J Theor Biol 219: 93–98. 12392978

109. Smolinski MS, Hamburg MA, Lederberg J, editors (2003) Microbial Threats to Health. Emergence, Detection and Response. Washington DC: The National Academies Press.

110. Rezelj VV, Levi LI, Vignuzzi M (2018) The defective component of viral populations. Curr Opin Virol 33: 74–80. doi: 10.1016/j.coviro.2018.07.014 30099321

111. Geoghegan JL, Holmes EC (2018) Evolutionary virology at 40. Genetics 210:1151–1162. doi: 10.1534/genetics.118.301556 30523166