Chapter 23 : Error Frequencies of Picornavirus RNA Polymerases: Evolutionary Implications for Virus Populations

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This chapter examines key features of the three main stages in virus evolution with examples drawn from several virus groups. It then reviews specific results with picornaviruses, as well as implications of high mutation rates and quasispecies dynamics for this important and diverse group of pathogens. With the levels of heterogeneity and viral load often seen in infected individuals, RNA virus populations include potentially all possible single mutants and decreasing amounts of multiple mutants. There are probably many routes to drug resistance, including amino acid replacements in the wall of the pocket preventing accommodation of the drug into the pocket (termed "exclusion" mutants), and replacements elsewhere in the capsid that affect viral uncoating. Resistant mutants display decreased affinity for the drug or increased affinity for the receptor, and often show low fitness values relative to their parental counterparts. Studies with picornaviral RNA-dependent RNA polymerases (replicases) face limitations derived from the difficulties in obtaining purified enzymes capable of sustaining multiple rounds of template-dependent copying. Viral quasispecies show features of complex adaptive systems such as mobilization of minority components (individual genomes from the mutant spectrum) in response to external stimuli. New developments in biochemistry and structural biology, and a deeper understanding of the principles governing viral evolution can now be combined to produce practical developments following an extensive (and necessary) accumulation of results from basic research.

Citation: Domingo E, Baranowski E, Escarmís C, Sobrino F, Holland J. 2002. Error Frequencies of Picornavirus RNA Polymerases: Evolutionary Implications for Virus Populations, p 285-298. In Semler B, Wimmer E (ed), Molecular Biology of Picornavirus. ASM Press, Washington, DC. doi: 10.1128/9781555817916.ch23

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Hepatitis C virus
Simian immunodeficiency virus
Foot-and-mouth disease virus
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1. Ahmad, A., L, A. B. Dowsett,, and D. A. Tyrrell. 1987. Studies of rhinovirus resistant to an antiviral chalcone. Antiviral Res. 8:2739.
2. Albiach-Marti, M. R.,, M. Mawassi,, S. Gowda,, T. Satyanarayana,, M. E. Hilf,, S. Shanker,, E. C. Almira,, M. C. Vives,, C. Lopez,, J. Guerri,, R. Flores,, P. Moreno,, S. M. Garnsey,, and W. O. Dawson. 2000. Sequences of Citrus Tristeza Virus separated in time and space are essentially identical. J. Virol. 74:68566865.
3. Anderson-Sillman, K.,, S. Bartal,, and D. R. Tershak. 1984. Guanidine-resistant poliovirus mutants produce modified 37-kilodalton proteins. J. Virol. 50:922928.
3a. Arias, A. E. Lázaro,, C. Escarmís,, and E. Domingo. 2001. Molecular intermediates of fitness gain of an RNA virus: characterization of a mutant spectrum by biological and molecular cloning. J. Gen. Virol. 82:10491060.
4. Arion, D.,, N. Kaushik,, S. McCormick,, G. Borkow,, and M. A. Parniak. 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. Biochemistry 37:1590815917.
5. Arnold, J. J.,, and C. E. Cameron. 2000. Poliovirus RNA-dependent RNA polymerase 3Dpol). Assembly of stable, elongation-competent complexes by using a symmetrical primer-template substrate (sym/sub). J. Biol. Chem. 275: 53295336.
6. Arnold, J. J.,, S. K. Ghosh,, and C. E. Cameron. 1999. Poliovirus RNA-dependent RNA polymerase (3Dpol). Divalent cation modulation of primer, template, and nucleotide selection. J. Biol. Chem. 274:3706037069.
7. Arts, E. J.,, and S. F. Le Grice. 1998. Interaction of retroviral reverse transcriptase with template-primer duplexes during replication. Prog. Nucleic Acid Res. Mol. Biol. 58:339393.
8. Bae, Y. S.,, and J. W. Yoon. 1993. Determination of diabetogenicity attributable to a single amino acid, Ala776, on the polyprotein of encephalomyocarditis virus. Diabetes 42:435443.
9. Bailly, J. L.,, M. Chambon,, C. Henquell,, J. Icart,, and H. Peigue-Lafeuille. 2000. Genomic variations in echovirus 30 persistent isolates recovered from a chronically infected immunodeficient child and comparison with the reference strain. J. Clin. Microbiol. 38:552557.
9a. Baranowski, E.,, C. M. Ruiz-Jarabo,, and E. Domingo. 2001. Evolution of cell recognition by viruses. Science 292:11021105.
10. Baranowski, E.,, C. M. Ruíz-Jarabo,, N. Sevilla,, D. Andreu,, E. Beck,, and E. Domingo. 2000. Cell recognition by foot-and-mouth disease virus that lacks the RGD integrin-binding motif: flexibility in aphthovirus receptor usage. J. Virol. 74:16411647.
11. Batschelet, E.,, E. Domingo,, and C. Weissmann. 1976. The proportion of revertant and mutant phage in a growing population, as a function of mutation and growth rate. Gene 1:2732.
12. Beard, C. W.,, and P. W. Mason. 2000. Genetic determinants of altered virulence of Taiwanese foot-and-mouth disease virus. J. Virol. 74:987991.
13. Bebenek, K.,, and T. A. Kunkel,. 1993. The fidelity ofretroviral reverse transcriptases, p. 85102. In A. M. Skalka, and S. P. Goff (ed.), Reverse Transcriptase. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.
14. Beck, E.,, and K. Strohmaier. 1987. Subtyping of European foot-and-mouth disease virus strains by nucleotide sequence determination. J. Virol. 61:16211629.
15. Beck, M. A.,, and O. A. Levander. 1997. Effects of nutritional antioxidants and other dietary constituents on coxsackievirus-induced myocarditis. Curr. Top. Microbiol. Immunol. 223:8196.
16. Beck, M. A.,, and O. A. Levander. 1995. Rapid genomic evolution of a non-virulent coxsackievirus B3 in selenium-deficient mice results in selection of identical virulent isolates. Nat. Med. 1:433436.
17. Bellmunt, A.,, G. May,, R. Zell,, P. Pring-Akerblom,, W. Verhagen,, and A. Heim. 1999. Evolution of poliovirus type I during 5.5 years of prolonged enteral replication in an immunodeficient patient. Virology 265:178184.
18. Belnap, D.M.,, B. M. McDermott, Jr.,, D. J. Filman,, N. Cheng,, B. L. Trus,, H. J. Zuccola,, V. R. Racaniello,, J. M. Hogle,, and A. C. Steven. 2000. Three-dimensional structure of poliovirus receptor bound to poliovirus. Proc. Natl. Acad. Sci. USA 97:7378.
19. Bernad, A.,, L. Blanco,, J. M. Lazaro,, G. Martin,, and M. Salas. 1989. A conserved 3' → 5' exonuclease active site in prokaryotic and eukaryotic DNA polymerases. Cell 59: 219228.
20. Biebricher, C.K., 1999. Mutation, competition and selectionas measured with small RNA molecules, p. 6585. In E. Domingo,, R. G. Webster,, and J. J. Holland (ed.), Origin and Evolution of Viruses. Academic Press, San Diego, Calif.
21. Boege, U.,, D. Kobasa,, S. Onodera,, G. D. Parks,, A. C. Palmenberg,, and D. G. Scraba. 1991. Characterization of mengo virus neutralization epitopes. Virology 181:113.
22. Borrego, B.,, I. S. Novella,, E. Giralt,, D. Andreu,, and E. Domingo. 1993. Distinct repertoire of antigenic variants of foot-and-mouth disease virus in the presence or absence of immune selection. J. Virol. 67:60716079.
23. Boyer, J. C.,, K. Bebenek,, and T. A. Kunkel. 1996. Analyzing the fidelity of reverse transcription and transcription. Methods Enzymol. 275:523537.
24. Brown, B.A.,, M. S. Oberste,, J. P. Alexander,Jr.,, M. L. Kennett,, and M. A. Pallansch. 1999. Molecular epidemiology and evolution of enterovirus 71 strains isolated from 1970 to 1998. J. Virol. 73:99699975.
25. Caggana, M.,, P. Chan,, and A. Ramsingh. 1993. Identification of a single amino acid residue in the capsid protein VP1 of coxsackievirus B4 that determines the virulent phenotype. J. Virol. 67:47974803.
26. Carrillo, C.,, M. Borca,, D. M. Moore,, D. O. Morgan,, and F. Sobrino. 1998. In vivo analysis of the stability and fitness of variants recovered from foot-and-mouth disease virus quasispecies. J. Gen. Virol. 79:16991706.
27. Carrillo, C.,, J. Plana,, R. Mascarella,, J. Bergada,, and F. Sobrino. 1990. Genetic and phenotypic variability during replication of foot-and-mouth disease virus in swine. Virology 179:890892.
28. Chao, L. 1990. Fitness of RNA virus decreased by Muller's ratchet. Nature 348:454455.
29. Chapman, N. M.,, A. I. Ramsingh,, and S. Tracy. 1997. Genetics of coxsackievirus virulence. Curr. Top. Microbiol. Immunol. 223:227258.
30. Chumakov, K. M.,, L. B. Powers,, K. E. Noonan,, I. B. Roninson,, and I. S. Levenbook. 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 88:199203.
31. Clarke, D. K.,, E. A. Duarte,, A. Moya,, S. F. Elena,, E. Domingo,, and J. Holland. 1993. Genetic bottlenecks and population passages cause profound fitness differences in RNA viruses. J. Virol. 67:222228.
32. Cowan, G. A.,, D. Pines,, and D. Meitzer (ed.). 1994. Complexity. Metaphors, Models and Reality. Addison-Wesley Publishing Company, Reading, Mass.
32a.. Crotty, S.,, C. E. Cameron,, and R. Andino. 2001. RNA virus error catastrophe: direct molecular test by using ribavirin. Proc. Natl. Acad. Sci. USA 98:68956900.
33. Crotty, S.,, D. Maag,, J. J. Arnold,, W. Zhong,, J. Y,. N. Lau,, Z. Hong,, R. Andino,, and C. E. Cameron. The broad-spectrum antiviral ribonucleotide, ribavirin, is an RNA virus mutagen. Nat. Med., in press.
34. Dasgupta, A.,, M. H. Baron,, and D. Baltimore. 1979. Poliovirus replicase: a soluble enzyme able to initiate copying of poliovirus RNA. Proc. Natl. Acad. Sci. USA 76:26792683.
35. Dearden, C.,, W. al-Nakib,, K. Andries,, R. Woestenborghs,, and D. A. Tyrrell. 1989. Drug resistant rhinoviruses from the nose of experimentally treated volunteers. Arch. Virol. 109:7181.
36. de la Torre, J. C.,, M. Davila,, F. Sobrino,, J. Ortín,, and E. Domingo. 1985. Establishment of cell lines persistently infected with foot-and-mouth disease virus. Virology 145:2435.
37. de la Torre, J. C.,, C. Giachetti,, B. L. Semler,, and J. J. Holland. 1992. High frequency of single-base transitions and extreme frequency of precise multiple-base reversion mutations in poliovirus. Proc. Natl. Acad. Sci. USA 89:25312535.
38. de la Torre, J. C.,, E. Martínez-Salas,, J. Diez,, A. Villaverde,, F. Gebauer,, E. Rocha,, M. Dávila,, and E. Domingo. 1988. Coevolution of cells and viruses in a persistent infection of foot-and-mouth disease virus in cell culture. J. Virol. 62:20502058.
39. de la Torre, J. C.,, E. Wimmer,, and J. J. Holland. 1990. Very high frequency of reversion to guanidine resistance in clonal pools of guanidine-dependent type 1 poliovirus. J. Virol. 64:664671.
40. Díez, J.,, M. Dávila,, C. Escarmís,, M. G. Mateu,, J. Dominguez,, J. J. Pérez,, E. Giralt,, J. A. Melero,, and E. Domingo. 1990. Unique amino acid substitutions in the capsid proteins of foot-and-mouth disease virus from a persistent infection in cell culture. J. Virol. 64:55195528.
41. Díez, J.,, M. G. Mateu,, and E. Domingo. 1989. Selection of antigenic variants of foot-and-mouth disease virus in the absence of antibodies, as revealed by an in situ assay. J. Gen. Virol. 70:32813289.
42. Domingo, E., 1999. Quasispecies, p. 14311436. In A. Granoff, and R. G. Webster (ed.), Encyclopedia of Virology. Academic Press, London, United Kingdom.
43. Domingo, E. 1989. RNA virus evolution and the control of viral disease. Prog. Drug Res. 33:93133.
44. Domingo, E., 1999. RNA virus quasispecies as models of biological complexity, p. 7990. In R. A. Dixon,, M. J. Harrison,, and M. J. Roossinck (ed.), Proceedings 10th Anniversary Symposium. The Samuel Roberts Noble Foundation, Plant Biology Division. The Samuel Roberts Foundation, Ardmore, Okla.
45. Domingo, E.,, C. Biebricher,, M. Eigen,, and J. J. Holland. 2001. Quasispecies and RNA Virus Evolution: Principles and Consequences. Landes Bioscience, Austin, Tex.
46. Domingo, E.,, J. Díez,, M. A. Martínez,, J. Hernández,, A. Holguín,, B. Borrego,, and M. G. Mateu. 1993. New observations on antigenic diversification of RNA viruses. Antigenic variation is not dependent on immune selection. J. Gen. Virol. 74:20392045.
47. Domingo, E.,, C. Escarmís,, L. Menéndez-Arias,, and J. J. Holland,. 1999. Viral quasispecies and fitness variations, p. 141161. In E. Domingo,, R. G. Webster,, and J. J. Holland (ed.), Origin and Evolution of Viruses. Academic Press, San Diego, Calif.
48. Domingo, E.,, and J. J. Holland,. 1994. Mutation rates and rapid evolution of RNA viruses, p. 161184. In S. S. Morse (ed.), Evolutionary Biology of Viruses. Raven Press, New York, N.Y.
49. Domingo, E.,, D. Sabo,, T. Taniguchi,, and C. Weissmann. 1978. Nucleotide sequence heterogeneity of an RNA phage population. Cell 13:735744.
50. Domingo, E.,, R. G. Webster,, and J. J. Holland (ed.). 1999. Origin and Evolution of Viruses. Academic Press, San Diego, Calif.
51. Drake, J. W. 1969. Comparative rates of spontaneous mutation. Nature 221:1132.
52. Drake, J. W. 1991. A constant rate of spontaneous mutation in DNA-based microbes. Proc. Natl. Acad. Sci. USA 88:71607164.
53. Drake, J. W.,, and J. J. Holland. 1999. Mutation rates among RNA viruses. Proc. Natl. Acad. Sci. USA 96: 1391013913.
54. Duarte, E.,, D. Clarke,, A. Moya,, E. Domingo,, and J. Holland. 1992. Rapid fitness losses in mammalian RNA virus clones due to Muller's ratchet. Proc. Natl. Acad. Sci. USA 89:60156019.
55. Duarte, E. A.,, D. K. Clarke,, A. Moya,, S. F. Elena,, E. Domingo,, and J. Holland. 1993. Many-trillionfold amplification of single RNA virus particles fails to overcome the Muller's ratchet effect. J. Virol. 67:36203623.
56. Eggers, H. J.,, and I. Tamm. 1965. Coxsackie A9 virus: mutation from drug dependence to drug independence. Science 148:9798.
57. Eigen, M. 1996. On the nature of virus quasispecies. Trends Microbiol. 4:216218.
58. Eigen, M. 1971. Self-organization of matter and the evolution of biological macromolecules. Naturwissenschaften 58:465523.
59. Eigen, M.,, and C. K. Biebricher,. 1988. Sequence space and quasispecies distribution, p. 211245. In E. Domingo,, P. Ahlquist,, and J. J. Holland (ed.), RNA Genetics, vol. 3. CRC Press, Boca Raton, Fla.
60. Elena, S. F.,, F. González-Candelas,, I. S. Novella,, E. A. Duarte,, D. K. Clarke,, E. Domingo,, J. J. Holland,, and A. Moya. 1996. Evolution of fitness in experimental populations of vesicular stomatitis virus. Genetics 142:673679.
61. Emini, E. A.,, B. A. Jameson,, A. J. Lewis,, G. R. Larsen,, and E. Wimmer. 1982. Poliovirus neutralization epitopes: analysis and localization with neutralizing monoclonal antibodies. J. Virol. 43:9971005.
62. Escarmís, C.,, E. C. Carrillo,, M. Ferrer,, J. F. Arriaza,, N. Lopez,, C. Tami,, N. Verdaguer,, E. Domingo,, and M. T. Franze-Fernández. 1998. Rapid selection in modified BHK-21 cells of a foot-and-mouth disease virus variant showing alterations in cell tropism. J. Virol. 72:1017110179.
63. Escarmís, C.,, M. Dávila,, N. Charpentier,, A. Bracho,, A. Moya,, and E. Domingo. 1996. Genetic lesions associated with Muller's ratchet in an RNA virus. J. Mol. Biol. 264: 255267.
64. Escarmís, C.,, M. Dávila,, and E. Domingo. 1999. Multiple molecular pathways for fitness recovery of an RNA virus debilitated by operation of Muller's ratchet. J. Mol. Biol. 285:495505.
65. Evans, D. J.,, and J. W. Almond. 1998. Cell receptors for picornaviruses as determinants of cell tropism and pathogenesis. Trends Microbiol. 6:198202.
66. Farci, P.,, A. Shimoda,, A. Coiana,, G. Diaz,, G. Peddis,, J. C. Melpolder,, A. Strazzera,, D. Y. Chien,, S. J. Munoz,, A. Balestrieri,, R. H. Purcell,, and H. J. Alter. 2000. The outcome of acute hepatitis C predicted by the evolution of the viral quasispecies. Science 288:339344.
67. Flanegan, J. B.,, and D. Baltimore. 1977. Poliovirus-specific primer-dependent RNA polymerase able to copy poly(A). Proc. Natl. Acad. Sci. USA 74:36773680.
68. Flanegan, J. B.,, and T. A. Van Dyke. 1979. Isolation of a soluble and template-dependent poliovirus RNA polymerase that copies virion RNA in vitro. J. Virol. 32:155161.
69. Flint, S. J.,, L. W. Enquist,, R. M. Krug,, V. R. Racaniello,, and A. M. Skalka. 2000. Virology. Molecular Biology, Pathogenesis and Control. ASM Press, Washington, D.C.
70. Forns, X.,, R. H. Purcell,, and J. Bukh. 1999. Quasispecies in viral persistence and pathogenesis of hepatitis C virus. Trends Microbiol. 7:402410.
71. Fox, M. P.,, M. J. Otto,, and M. A. McKinlay. 1986. The prevention of rhinovirus and poliovirus uncoating by WIN 51711: a new antiviral drug. Antimicrob. Agents Chemother. 30:110116.
72. Fry, E. E.,, S. M. Lea,, T. Jackson,, J. W. Newman,, F. M. Ellard,, W. E. Blakemore,, R. Abu-Ghazaleh,, A. Samuel,, A. M. King,, and D. I. Stuart. 1999. The structure and function of a foot-and-mouth disease virus-oligosaccharide receptor complex. EMBO J. 18:543554.
73. Gauntt, C. J. 1997. Roles of the humoral response in coxsackievirus B-induced disease. Curr. Top. Microbiol. Immunol. 223:259282.
74. Gavrilin, G. V.,, E. A. Cherkasova,, G. Y. Lipskaya,, O. M. Kew,, and V. I. Agol. 2000. Evolution of circulating wild poliovirus and of vaccine-derived poliovirus in an immunodeficient patient: a unifying model. J. Virol. 74: 73817390.
75. Gebauer, F.,, J. C. de la Torre,, I. Gomes,, M. G. Mateu,, H. Barahona,, B. Tiraboschi,, I. Bergmann,, P. A. de Mello,, and E. Domingo. 1988. Rapid selection of genetic and antigenic variants of foot-and-mouth disease virus during persistence in cattle. J. Virol. 62:20412049.
76. Gell-Mann, M. 1994. The Quark and the Jaguar. Freeman, New York, N.Y.
77. Gibbs, A.,, C. Calisher,, and F. García-Arenal (ed.). 1995. Molecular Basis of Virus Evolution. Cambridge University Press, Cambridge, United Kingdom.
78. Giraudo, A. T.,, E. Beck,, K. Strebel,, P. A. de Mello,, J. L. La Torre,, E. A. Scodeller,, and I. E. Bergmann. 1990. Identification of a nucleotide deletion in parts of polypeptide 3A in two independent attenuated aphthovirus strains. Virology 177:780783.
79. Gohara, D. W.,, S. Crotty,, J. J. Arnold,, J. D. Yoder,, R. Andino,, and C. E. Cameron. 2000. Poliovirus RNA-dependent RNA polymerase (3Dpol). Structural, biochemical, and biological analysis of conserved structural motifs A and B. J. Biol. Chem. 275:2552325532.
80. González, M. J.,, J. C. Sáiz,, O. Laor,, and D. M. Moore. 1981. Antigenic stability of foot-and-mouth disease virus variants on serial passage in cell culture. J. Virol. 65: 39493953.
81. Goodman, M. F.,, and K. D. Fygenson. 1998. DNA polymerase fidelity: from Genetics toward a biochemical understanding. Genetics 148:14751482.
82. Gromeier, M.,, E. Wimmer,, and A. E. Gorbalenya,. 1999. Genetics, pathogenesis and evolution of picornaviruses, p. 287343. In E. Domingo,, R. G. Webster,, and J. J. Holland (ed.), Origin and Evolution of Viruses. Academic Press, San Diego, Calif.
83. Hadfield, A. T.,, M. A. Oliveira,, K. H. Kim,, P. Minor,, M. Kremer,, B. A. Heinz,, D. Shepard,, D. C. Pevear,, R. R. Rueckert,, and M. G. Rossmann. 1995. Structural studies on human rhinovirus 14 drug-resistant compensation mutants. J. Mol. Biol. 253:6173.
84. Hansen, J.,, A. M. Long,, and S. Schultz. 1997. Structure of the RNA-dependent RNA polymerase of poliovirus. Structure 15:11091122.
85. Harber, J.,, G. Bernhardt,, H. H. Lu,, J. Y. Sgro,, and E. Wimmer. 1995. Canyon rim residues, including antigenic determinants, modulate serotype-specific binding of polioviruses to mutants of the poliovirus receptor. Virology 214:559570.
86. He, Y.,, V. D. Bowman,, S. Mueller,, C. M. Bator,, J. Bella,, X. Peng,, T. S. Baker,, E. Wimmer,, R. J. Kuhn,, and M. G. Rossmann. 2000. Interaction of the poliovirus receptor with poliovirus. Proc. Natl. Acad. Sci. USA 97:7984.
87. Heinz, B. A.,, R. R. Rueckert,, D. A. Shepard,, F. J. Dutko,, M. A. McKinlay,, M. Fancher,, M. G. Rossmann,, J. Badger,, and T. J. Smith. 1989. Genetic and molecular analyses of spontaneous mutants of human rhinovirus 14 that are resistant to an antiviral compound. J. Virol. 63: 24762485.
88. Hernández, J.,, M. A. Martínez,, E. Rocha,, E. Domingo,, and M. G. Mateu. 1992. Generation of a subtype-specific neutralization epitope in foot-and-mouth disease virus of a different subtype. J. Gen. Virol. 73:213216.
89. Hewat, E. A.,, N. Verdaguer,, I. Fita,, W. Blakemore,, S. Brookes,, A. King,, J. Newman,, E. Domingo,, M. G. Mateu,, and D. I. Stuart. 1997. Structure of the complex of an Fab fragment of a neutralizing antibody with foot-and-mouth disease virus: positioning of a highly mobile antigenic loop. EMBO J. 16:14921500.
90. Hirasawa, K.,, H. S. Jun,, H. S. Han,, M. L. Zhang,, M. D. Hollenberg,, and J. W. Yoon. 1999. Prevention of encephalomyocarditis virus-induced diabetes in mice by inhibition of the tyrosine kinase signalling pathway and subsequent suppression of nitric oxide production in macrophages. J. Virol. 73:85418548.
91. Holland, J.,, K. Spindler,, F. Horodyski,, E. Grabau,, S. Nichol,, and S. VandePol. 1982. Rapid evolution of RNA genomes. Science 215:15771585.
92. Holland, J. J. (ed.). 1992. Genetic diversity of RNA viruses. Curr. Top. Microbiol. Immunol., vol. 176.
93. Holland, J. J.,, J. C. de la Torre,, D. K. Clarke,, and E. Duarte. 1991. Quantitation of relative fitness and great adaptability of clonal populations of RNA viruses. J. Virol. 65:29602967.
94. Holland, J. J.,, J. C. de La Torre,, and D. A. Steinhauer. 1992. RNA virus populations as quasispecies. Curr. Top. Microbiol. Immunol. 176:120.
95. Holland, J. J.,, J. C. de la Torre,, D. A. Steinhauer,, D. Clarke,, E. Duarte,, and E. Domingo. 1989. Virus mutation frequencies can be greatly underestimated by monoclonal antibody neutralization of virions. J. Virol. 63:50305036.
96. Holland, J. J.,, E. Domingo,, J. C. de la Torre,, and D. A. Steinhauer. 1990. Mutation frequencies at defined single codon sites in vesicular stomatitis virus and poliovirus can be increased only slightly by chemical mutagenesis. J. Virol. 64:39603962.
97. Hyypiä, T.,, T. Hovi,, N. J. Knowles,, and G. Stanway. 1997. Classification of enteroviruses based on molecular and biological properties. J. Gen. Virol. 78:111.
98. Jackson, T.,, F. M. Ellard,, R. A. Ghazaleh,, S. M. Brookes,, W. E. Blakemore,, A. H. Corteyn,, D. I. Stuart,, J. W. Newman,, and A. M. King. 1996. Efficient infection of cells in culture by type O foot-and-mouth disease virus requires binding to cell surface heparan sulfate. J. Virol. 70:52825287.
99. Jnaoui, K.,, and T. Middels. 1998. Adaptation of Theiler's virus to L929 cells: mutations in the putative receptor binding site on the capsid map to neutralization sites and modulate viral persistence. Virology 244:397404.
100. Kew, O. M.,, R. W. Sutter,, B. K. Nottay,, M. J. McDenough,, R. Prevots,, L. Quick,, and M. A. Pallansch. 1995. Molecular epidemiology of poliovirus. Semin. Virol. 6:401414.
100a.. Kew, O.,, V. Morris-Glasgow,, M. Landaverde,, C. Burns,, J. Shaw,, Z. Garib,, J. Andre,, E. Blackman,, C. J. Freeman,, J. Jorba,, R. Sutter,, G. Tambini,, L. Venczel,, C. Perdreira,, F. Laender,, H. Shimizu,, T. Yoneyama,, T. Miyamura,, H. van der Avoort,, M. S. Oberste,, D. Kilpatrick,, S. Cochi,, M. Pallansch,, and C. de Quadros. 2002. Outbreak of poliomyelitis in Hispaniola associated with circulating type 1 vaccine-derived poliovirus. Science 296:356359.
101. Kew, O. M.,, R. W. Sutter,, B. K Nottay,, M. J. McDonough,, D. R. Prevots,, L. Quick,, and M. A. Pallansch. 1998. Prolonged replication of a type 1 vaccine-derived poliovirus in an immunodeficient patient. J. Clin. Microbiol. 36:28932899.
102. Kilbourne, E. D., 1994. Host determination of viral evolution: a variable tautology, p. 253271. In S. S. Morse (ed.), The Evolutionary Biology of Viruses. Raven Press, New York, N.Y.
103. King, A. M.,, D. McCahon,, W. R. Slade,, and J. W. Newman. 1982. Recombination in RNA. Cell 29:921928.
104. Kolatkar, P. R.,, J. Bella,, N. H. Olson,, C. M. Bator,, T. S. Baker,, and M. G. Rossmann. 1999. Structural studies of two rhinovirus serotypes complexed with fragments of their cellular receptor. EMBO J. 18:62496259.
105. Kuge, S.,, N. Kawamura,, and A. Nomoto. 1989. Strong inclination toward transition mutation in nucleotide substitutions by poliovirus replicase. J. Mol. Biol. 207: 175182.
106. Lai, M. M. C., 1995. Recombination and its evolutionary effects on viruses with RNA genomes, p. 119132. In A. Gibbs (ed.), Molecular Basis of Virus Evolution. Cambridge University Press, Cambridge, United Kingdom.
107. Lea, S.,, J. Hernández,, W. Blakemore,, E. Brocchi,, S. Curry,, E. Domingo,, E. Fry,, R. Abu-Ghazaleh,, A. King,, J. Newman,, D. Stuart,, and M. G. Mateu. 1994. The structure and antigenicity of a type C foot-and-mouth disease virus. Structure 2:123139.
108. Ledinko, N. 1963. Genetic recombination with poliovirus type 1. Studies of crosses between a normal horse serum-resistant mutant and several guanidine-resistant mutants of the same strain. Virology 20:107119.
109. Lemon, S. M.,, L. Whetter,, K. H. Chang,, and E. A. Brown. 1992. Why do human hepatitis viruses replicate so poorly in cell cultures? FEMS Microbiol. Lett. 79:455459.
110. Li, F.,, G. F. Browning,, M. J. Studdert,, and B. S. Crabb. 1996. Equine rhinovirus 1 is more closely related to foot-and-mouth disease virus than to other picornaviruses. Proc. Natl. Acad. Sci. USA 93:990995.
111. Liao, S.,, and V. Racaniello. 1997. Allele-specific adaptation of poliovirus VP1 B-C loop variants to mutant cell receptors. J. Virol. 71:97709777.
112. Loeb, L. A., , J. M. Essigmann,, F. Kazazi,, J. Zhang,, K. D. Rose,, and J. I. Mullins. 1999. Lethal mutagenesis of HIV with mutagenic nucleoside analogs. Proc. Natl. Acad. Sci. USA 96:14921497.
113. Loeb, L. A., , and J. I. Mullins. 2000. Lethal mutagenesis of HIV by mutagenic ribonucleoside analogs. AIDS Res. Hum. Retrovir. 13:13.
114. Mansky, L. M. 1996. The mutation rate of human immunodeficiency virus type 1 is influenced by the vpr gene. Virology 222:391400.
115. Mansky, L. M.,, S. Preveral,, L. Selig,, R. Benarous,, and S. Benichou. 2000. The interaction of Vpr with uracil DNA glycosylase modulates the human immunodeficiency virus type 1 in vivo mutation rate. J. Virol. 74: 70397047.
116. Martin, B., 1994 The schema, p. 263285. In G. A. Cowan,, D. Pines,, and D. Meitzer (ed.), Complexity. Metaphors, Models and Reality. Addison Wesley Publishing Co., Reading, Mass.
117. Martin, J.,, G. Dunn,, R. Hull,, V. Patel,, and P. D. Minor. 2000. Evolution of the Sabin strain of type 3 poliovirus in an immunodeficient patient during the entire 637-day period of virus excretion. J. Virol. 74:30013010.
118. Martínez, M. A.,, C. Carrillo,, F. González-Candelas,, A. Moya,, E. Domingo,, and F. Sobrino. 1991. Fitness alteration of foot-and-mouth disease virus mutants: measurement of adaptability of viral quasispecies. J. Virol. 65: 39543957.
119. Martínez, M. A.,, N. Verdaguer,, M. G. Mateu,, and E. Domingo. 1997. Evolution subverting essentiality: dispensability of the cell attachment Arg-Gly-Asp motif in multiply passaged foot-and-mouth disease virus. Proc. Natl. Acad. Sci. USA 94:67986802.
120. Martínez-Salas, E.,, J. Ortín,, and E. Domingo. 1985. Sequence of the viral replicase gene from foot-and-mouth disease virus Cl-Santa Pau (C-S8). Gene 35:5561.
121. Martin-Hernández, A. M.,, E. Domingo,, and L. Menéndez-Arias. 1996. Human immunodeficiency virus type 1 reverse transcriptase: role of Tyr115 in deoxynucleotide binding and misinsertion fidelity of DNA synthesis. EMBO J. 15:44344442.
122. Marvil, P.,, N. J. Knowles,, A. P. Mockett,, P. Britton,, T. D. Brown,, and D. Cavanagh. 1999. Avian encephalomyelitis virus is a Picornavirus and is most closely related to hepatitis A virus. J. Gen. Virol. 80:653662.
123. Mas, A.,, M. Parera,, C. Briones,, V. Soriano,, M. A. Martínez,, E. Domingo,, and L. Menéndez-Arias. 2000. Role of a dipeptide insertion between codons 69-70 of HIV-1 reverse transcriptase in the mechanism of AZT resistance. EMBO J. 19:57525761.
124. Mateu, M. G. 1995. Antibody recognition of picornaviruses and escape from neutralization: a structural view. Virus Res. 38:124.
125. Mateu, M. G.,, C. Escarmís,, and E. Domingo. 1998. Mutational analysis of discontinuous epitopes of foot-and-mouth disease virus using an unprocessed capsid pro-tomer precursor. Virus Res. 53:2737.
126. Melnick, J. L.,, D. Crowther,, and J. Barrera-Oro. 1961. Rapid development of drug-resistant mutants of poliovirus. Science 134:557.
127. Meyer, P. R.,, S. E. Matsuura,, A. M. Mian,, A. G. So,, and W. A. Scott. 1999. A mechanism of AZT resistance: an increase in nucleotide-dependent primer unblocking by mutant HIV-1 reverse transcriptase. Mol. Cell 4:3543.
128. Meyerhans, A.,, and J.-P. Vartanian,. 1999. The fidelity of cellular and viral polymerases and its manipulation for hypermutagenesis, p. 87114. In E. Domingo,, R. G. Webster,, and J. J. Holland (ed.), Origin and Evolution of Viruses. Academic Press, San Diego, Calif.
129. Minor, P. D. 1992. The molecular biology of poliovaccines. J. Gen. Virol. 73:30653077.
130. Minor, P. D.,, M. Ferguson,, D. M. Evans,, J. W. Almond,, and J. P. Icenogle. 1986. Antigenic structure of polioviruses of serotypes 1, 2 and 3. J. Gen. Virol. 67: 12831291.
131. Minor, P. D.,, G. C. Schild,, J. Bootman,, D. M. Evans,, M. Ferguson,, P. Reeve,, M. Spitz,, G. Stanway,, A. J. Cann,, R. Hauptmann,, L. D. Clarke,, R. C. Mountford,, and J. W. Almond. 1983. Location and primary structure of a major antigenic site for poliovirus neutralization. Nature 301:674679.
132. Misbah, S. A., , G. P. Spickett,, P. C. Ryba,, J. M. Hockaday,, J. S. Kroll,, C. Sherwood,, J. B. Kurtz,, E. R. Moxon,, and H. M. Chapel. 1992. Chronic enteroviral meningoencephalitis in agammaglobulinemia: case report and literature review. J. Clin. Immunol. 12:266270.
133. Morse, S. S. (ed.). 1993. Emerging Viruses. Oxford University Press, Oxford, United Kingdom.
134. Morse, S. S. (ed.). 1994. The Evolutionary Biology of Viruses. Raven Press, New York, N.Y.
135. Mosser, A. G.,, and R. R. Rueckert,. 1996. Capsid-binding agents, p. 1340. In D. D. Richman (ed.), Antiviral Drug Resistance. John Wiley and Sons Ltd., Chichester, United Kingdom.
136. Mosser, A. G.,, J. Y. Sgro,, and R. R. Rueckert. 1994. Distribution of drug resistance mutations in type 3 poliovirus identifies three regions involved in uncoating functions. J. Virol. 68:81938201.
137. Murphy, F. A.,, and N. Nathanson. 1994. The emergence of new virus diseases: an overview. Semin. Virol. 5:87102.
138. Nagy, P. D.,, and A. E. Simon. 1997. New insights into the mechanisms of RNA recombination. Virology 235: 19.
139. Nájera, I.,, A. Holguín,, M. E. Quiñones-Mateu,, M. A. Muñoz-Fernández,, R. Nájera,, C. López-Galíndez,, and E. Domingo. 1995. Pol gene quasispecies of human immunodeficiency virus: mutations associated with drug resistance in virus from patients undergoing no drug therapy. J. Virol. 69:2331.
140. Nomoto, A.,, T. Omata,, H. Toyoda,, S. Kuge,, H. Horie,, Y. Kataoka,, Y. Genba,, Y. Nakano,, and N. Imura. 1982. Complete nucleotide sequence of the attenuated poliovirus Sabin 1 strain genome. Proc. Natl. Acad. Sci. USA 79:57935797.
141. Novella, I. S.,, E. A. Duarte,, S. F. Elena,, A. Moya,, E. Domingo,, and J. J. Holland. 1995. Exponential increases of RNA virus fitness during large population transmissions. Proc. Natl. Acad. Sci. USA 92:58415844.
142. Novella, I. S.,, S. F. Elena,, A. Moya,, E. Domingo,, and J. J. Holland. 1995. Size of genetic bottlenecks leading to virus fitness loss is determined by mean initial population fitness. J. Virol. 69:28692872.
143. Novella, I. S.,, C. L. Hershey,, C. Escarmís,, E. Domingo,, and J. J. Holland. 1999. Lack of evolutionary stasis during alternating replication of an arbovirus in insect and mammalian cells. J. Mol. Biol. 287:459465.
144. Novella, I. S.,, J. Quer,, E. Domingo,, and J. J. Holland. 1999. Exponential fitness gains of RNA virus populations are limited by bottleneck effects. J. Virol. 73:16681671.
145. Nowak, M. A. 1992. What is a quasispecies? Trends Ecol. Evol. 4:118121.
145a.. Núñez, J. L.,, E. Baranowski,, N. Molina,, C. M. Ruíz-Jarabo,, C. Sanchez,, E. Domingo,, and F. Sobrino. 2001. A single amino acid substitution in nonstructural protein 3A can mediate adaptation of foot-and-mouth disease virus to the guinea pig. J. Virol. 75:39773983.
145b.. Pariente, N.,, S. Sierra,, P. R. Lowenstein,, and E. Domingo. 2001. Efficient vims extinction by combinations of a mutagen and antiviral inhibitors. J. Virol. 75: 97239730.
146. Parvin, J. D.,, A. Moscona,, W. T. Pan,, J. M. Leider,, and P. Palese. 1986. Measurement of the mutation rates of animal viruses: influenza A virus and poliovirus type 1. J. Virol. 59:377383.
147. Pathak, V. K.,, and H. M. Temin. 1992. 5-Azacytidine and RNA secondary structure increase the retrovirus mutation rate. J. Virol. 66:30933100.
148. Patterson, L. J.,, and V. V. Hamparian. 1997. Hyperantigenic variation occurs with human rhinovirus type 17. J. Virol. 71:13701374.
149. Paul, A. V.,, J. H. van Boom,, D. Filippov,, and E. Wimmer. 1998. Protein-primed RNA synthesis by purified poliovirus RNA polymerase. Nature 393:280284.
149a.. Pawlotsky, J. M. 2000. Hepatitis C. Virus Resistance to antiviral therapy. Hepatology 32:889896.
150. Pawlotsky, J. M.,, G. Germanidis,, A. U. Neumann,, M. Pellerin,, P. O. Frainais,, and D. Dhumeaux. 1998. Interferon resistance of hepatitis C virus genotype lb: relationship to nonstructural 5A gene quasispecies mutations. J. Virol 72:27952805.
151. Pfister, T.,, and E. Wimmer. 1999. Characterization of the nucleoside triphosphatase activity of poliovirus protein 2C reveals a mechanism by which guanidine inhibits poliovirus replication. J. Biol. Chem. 274:69927001.
152. Pincus, S. E.,, and E. Wimmer. 1986. Production of guanidine-resistant and -dependent poliovirus mutants from cloned cDNA: mutations in polypeptide 2C are directly responsible for altered guanidine sensitivity. J. Virol. 60:793796.
153. Prabhakar, B. S.,, V. M. Haspel,, P. R. McClintock,, and A. L. Notkins. 1982. High frequency of antigenic variants among naturally occurring human coxsackie B4 virus isolates identified by monoclonal antibodies. Nature 300:374376.
154. Prabhakar, B. S.,, M. A. Menegus,, and A. L. Notkins. 1985. Detection of conserved and nonconserved epitopes on coxsackievirus B4: frequency of antigenic change. Virology 146:302306.
155. Racaniello, V. R.,, and D. Baltimore. 1981. Cloned poliovirus complementary DNA is infectious in mammalian cells. Science 214:916919.
156. Ramsingh, A. I.,, and D. N. Collins. 1995. A point mutation in the VP4 coding sequence of coxsackievirus B4 influences virulence. J. Virol. 69:72787281.
157. Ramsingh, A. I., , W. T. Lee,, D. N. Collins,, and L. E. Armstrong. 1999. T cells contribute to disease severity during coxsackievirus B4 infection. J. Virol. 73:30803086.
158. Rodrigo, M. J.,, and J. Dopazo. 1995. Evolutionary analysis of the Picornavirus family. J. Mol. Evol. 40:362371.
159. Rossmann, M. G.,, J. Bella,, P. R. Kolatkar,, Y. He,, E. Wimmer,, R. Kuhn,, and T. S. Baker. 2000. Cell recognition and entry by rhino- and enteroviruses. Virology 269:239247.
160. Ruiz-Jarabo, C. M.,, A. Arias,, E. Baranowski,, C. Escarmís,, and E. Domingo. 2000. Memory in viral quasispecies. J. Virol. 74:35433547.
160a.. Ruiz-Jarabo, C. M.,, A. Arias,, C. Molina-Paris,, C. Briones,, E. Baranowski,, C. Escarmís,, and E. Domingo. 2002. Duration and fitness dependence of quasispecies memory. J. Mol. Biol. 315:285296.
161. Ruiz-Jarabo, C. M.,, N. Sevilla,, M. Davila,, G. Gomez-Mariano,, E. Baranowski,, and E. Domingo. 1999. Antigenic properties and population stability of a foot-and-mouth disease virus with an altered Arg-Gly-Asp receptor-recognition motif. J. Gen. Virol. 80:18991909.
162. Sa-Carvalho, D.,, E. Rieder,, B. Baxt,, R. Rodarte,, A. Tanuri,, and P. W. Mason. 1997. Tissue culture adaptation of foot-and-mouth disease virus selects viruses that bind to heparin and are attenuated in cattle. J. Virol. 71: 51155123.
163. Sáiz, J. C., and E. Domingo. 1996. Virulence as a positive trait in viral persistence. J. Virol. 70:64106413.
164. Sankar, S.,, and A. G. Porter. 1992. Point mutations which drastically affect the polymerization activity of encephalomyocarditis virus RNA-dependent RNA polymerase correspond to the active site of Escherichia coli DNA polymerase I. J. Biol. Chem. 267:1016810176.
165. Saunders, K.,, and A. M. King. 1982. Guanidine-resistant mutants of aphthovirus induce the synthesis of an altered nonstructural polypeptide, P34. J. Virol. 42: 389394.
166. Schrag, S. J.,, P. A. Rota,, and W. J. Bellini. 1999. Spontaneous mutation rate of measles virus: direct estimation based on mutations conferring monoclonal antibody resistance. J. Virol. 73:5154.
167. Schwimmbeck, P. L.,, S. A. Huber,, and H. P. Schultheiss. 1997. Roles of T cells in coxsackievirus B-induced disease. Curr. Top. Microbiol. Immunol. 223:283303.
168. Sedivy, J. M.,, J. P. Capone,, U. L. RajBhandary,, and P. A. Sharp. 1987. An inducible mammalian amber suppressor: propagation of a poliovirus mutant. Cell 50:379389.
169. Sevilla, N.,, and E. Domingo. 1996. Evolution of a persistent aphthovirus in cytolytic infections: partial reversion of phenotypic traits accompanied by genetic diversification. J. Virol. 70:66176624.
170. Sevilla, N.,, C. M. Ruiz-Jarabo,, G. Gómez-Mariano,, E. Baranowski,, and E. Domingo. 1998. An RNA virus can adapt to the multiplicity of infection. J. Gen. Virol. 79: 29712980.
171. Sevilla, N.,, N. Verdaguer,, and E. Domingo. 1996. Antigenically profound amino acid substitutions occur during large population passages of foot-and-mouth disease virus. Virology 225:400405.
172. Sherry, B.,, A. G. Mosser,, R. J. Colonno,, and R. R. Rueckert. 1986. Use of monoclonal antibodies to identify four neutralization immunogens on a common cold Picornavirus, human rhinovirus 14. J. Virol. 57: 246257.
173. Sierra, S.,, M. Dávila,, P. R. Lowenstein,, and E. Domingo. 2000. Response of foot-and-mouth disease virus to increased mutagenesis. Influence of viral load and fitness in loss of infectivity. J. Virol. 74:83168323.
174. Smith, T. J.,, and T. Baker. 1999. Picornaviruses: epitopes, canyons, and pockets. Adv. Virus Res. 52:123.
175. Smith, T. J.,, E. S. Chase,, T. J. Schmidt,, N. H. Olson,, and T. S. Baker. 1996. Neutralizing antibody to human rhinovirus 14 penetrates the receptor-binding canyon. Nature 383:350354.
176. Smith, T. J.,, M. J. Kremer,, M. Luo,, G. Vriend,, E. Arnold,, G. Kamer,, M. G. Rossmann,, M. A. McKinlay,, G. D. Diana,, and M. J. Otto. 1986. The site of attachment in human rhinovirus 14 for antiviral agents that inhibit uncoating. Science 233:12861293.
177. Sousa, R. 1996. Structural and mechanistic relationships between nucleic acid polymerases. Trends Biochem. Sci. 21:186190.
178. Stanway, G.,, P. J. Hughes,, R. C. Mountford,, P. Reeve,, P. D. Minor,, G. C. Schild,, and J. W. Almond. 1984. Comparison of the complete nucleotide sequences of the genomes of the neurovirulent poliovirus P3/Leon/37 and its attenuated Sabin vaccine derivative P3/Leon 12alb. Proc. Natl. Acad. Sci. USA 81:15391543.
179. Stapleton, J. T.,, and S. M. Lemon. 1987. Neutralization escape mutants define a dominant immunogenic neutralization site on hepatitis A virus. J. Virol. 61:491498.
180. Steinhauer, D. A.,, J. C. de la Torre,, and J. J. Holland. 1989. High nucleotide substitution error frequencies in clonal pools of vesicular stomatitis virus. J. Virol. 63:20632071.
181. Steinhauer, D. A., , E. Domingo,, and J. J. Holland. 1992. Lack of evidence for proofreading mechanisms associated with an RNA virus polymerase. Gene 122:281288.
182. Steinhauer, D. A., , and J. J. Holland. 1986. Direct method for quantitation of extreme polymerase error frequencies at selected single base sites in viral RNA. J. Virol. 57:219228.
183. Steitz, T. A. 1999. DNA polymerases: structural diversity and common mechanisms. J. Biol. Chem. 274:1739517398.
184. Taboga, O.,, C. Tami,, E. Carrillo,, J., I. Nuñez,, A. Rodriguez,, J. C. Saíz,, E. Blanco,, M. L. Valero,, X. Roig,, J. A. Camarero,, D. Andreu,, M. G. Mateu,, E. Giralt,, E. Domingo,, F. Sobrino,, and E. L. Palma. 1997. A large-scale evaluation of peptide vaccines against foot-and-mouth disease: lack of solid protection in cattle and isolation of escape mutants. J. Virol. 71:26062614.
185. Tatem, J. M.,, C. Weeks-Levy,, A. Georgiu,, S. J. Di-Michele,, E. J. Gorgacz,, V. R. Racaniello,, F. R. Cano,, and S. J. Mento. 1992. A mutation present in the amino terminus of Sabin 3 poliovirus VP1 protein is attenuating. J. Virol. 66:31943197.
186. Tu, Z.,, N. M. Chapman,, G. Hufnagel,, S. Tracy,, J. R. Romero,, W. H. Barry,, L. Zhao,, K. Currey,, and B. Shapiro. 1995. The cardiovirulent phenotype of coxsackievirus B3 is determined at a single site in the genomic 5' nontranslated region. J. Virol. 69:46074618.
187. Tyrrell, D. A. 1988. Hot news on the common cold. Annu. Rev. Microbiol. 42:3547.
188. Usherwood, E. J.,, and A. A. Nash. 1995. Lymphocyte recognition of picornaviruses. J. Gen. Virol. 76:499508.
189. Valcarcel, J.,, and J. Ortin. 1989. Phenotypic hiding: the carryover of mutations in RNA viruses as shown by detection of mar mutants in influenza virus. J. Virol. 63: 41074109.
190. Verdaguer, N.,, M. G. Mateu,, D. Andreu,, E. Giralt,, E. Domingo,, and I. Fita. 1995. Structure of the major antigenic loop of foot-and-mouth disease virus complexed with a neutralizing antibody: direct involvement of the Arg-Gly-Asp motif in the interaction. EMBO J. 14: 16901696.
191. Verdaguer, N.,, M. G. Mateu,, J. Bravo,, E. Domingo,, and I. Fita. 1996. Induced pocket to accommodate the cell attachment Arg-Gly-Asp motif in a neutralizing antibody against foot-and-mouth-disease virus. J. Mol. Biol. 256:364376.
192. Verdaguer, N.,, N. Sevilla,, M. L. Valero,, D. Stuart,, E. Brocchi,, D. Andreu,, E. Giralt,, E. Domingo,, M. G. Mateu,, and I. Fita. 1998. A similar pattern of interaction for different antibodies with a major antigenic site of foot-and-mouth disease virus: implications for intratypic antigenic variation. J. Virol. 72:739748.
193. Villaverde, A.,, E. Martínez-Salas,, and E. Domingo. 1988. 3D gene of foot-and-mouth disease virus. Conservation by convergence of average sequences. J. Mol. Biol. 204:771776.
194. Volkenstein, M. V. 1994. Physical Approaches to Biological Evolution. Springer-Verlag, Berlin, Germany.
195. Wainberg, M. A.,, W. C. Drosopoulos,, H. Salomon,, M. Hsu,, G. Borkow,, M. Parniak,, Z. Gu,, Q. Song,, J. Manne,, S. Islam,, G. Castriota,, and V. R. Prasad. 1996. Enhanced fidelity of 3TC-selected mutant HIV-1 reverse transcriptase. Science 271:12821285.
196. Ward, C. D.,, and J. B. Flanegan. 1992. Determination of the poliovirus RNA polymerase error frequency at eight sites in the viral genome. J. Virol. 66:37843793.
197. Ward, C. D.,, M. A. Stokes,, and J. B. Flanegan. 1988. Direct measurement of the poliovirus RNA polymerase error frequency in vitro. J. Virol. 62:558562.
198. Weaver, S. C.,, A. C. Brauk,, W. Kang,, and J. J. Holland. 1999. Genetic and fitness changes accompanying adaptation of an arbovirus to vertebrate and invertebrate cells. J. Virol. 73:43164326.
199. Webster, R. G., 1999. Antigenic variation in influenza viruses, p. 377390. In E. Domingo,, R. G. Webster,, and J. J. Holland (ed.), Origin and Evolution of Viruses. Academic Press, San Diego, Calif.
199a.. Wells, V. R.,, S. J. Plotch,, and J. J. DeStefano. 2001. Determination of the mutation rate of poliovirus RNA-dependent RNA polymerase. Virus Res. 74:119132.
200. Wimmer, E.,, C. U. Hellen,, and X. Cao. 1993. Genetics of poliovirus. Annu. Rev. Genet. 27:353436.
201. Wutz, G.,, H. Auer,, N. Nowotny,, B. Grosse,, T. Skern,, and E. Kuechler. 1996. Equine rhinovirus serotypes 1 and 2: relationship to each other and to aphthoviruses and cardioviruses. J. Gen. Virol. 77:17191730.
202. Xie, Q.-C.,, D. McCahon,, J. R. Crowther,, G. J. Belsham,, and K. C. McCullough. 1987. Neutralization of foot-and-mouth disease virus can be mediated through any of at least three separate antigenic sites. J. Gen. Virol. 68:16371647.
203. Xing, L.,, K. Tjarnlund,, B. Lindqvist,, G. G. Kaplan,, D. Feigelstock,, R. H. Cheng,, and J. M. Casasnovas. 2000. Distinct cellular receptor interactions in poliovirus and rhinoviruses. EMBO J. 19:12071216.
204. Yoon, J. W,, and H. S. Jun,. 1998. Insulin-dependent diabetes mellitus, p. 1390-1398. In I. M. Roitt, and P. J. Delves (ed.), Encyclopedia of Immunology, 2nd ed. Academic Press, London, United Kingdom.
205. Yuste, E.,, C. López-Galíndez,, and E. Domingo. 2000. Unusual distribution of mutations associated with serial bottleneck passages of human immunodeficiency virus type 1. J. Virol. 74:95469552.
206. Yuste, E.,, S. Sánchez-Palomino,, C. Casado,, E. Domingo,, and C. López-Galíndez. 1999. Drastic fitness loss in human immunodeficiency virus type 1 upon serial bottleneck events. J. Virol. 73:27452751.
207. Zhang, G.,, G. Wilsden,, N. J. Knowles,, and J. W. McCauley. 1993. Complete nucleotide sequence of a Coxsackie B5 virus and its relationship to swine vesicular disease virus. J. Gen. Virol. 74:845853.
208. Zhang,, Zimmern, D., 1988. Evolution of RNA viruses, p. 211240. In E. Domingo,, J. J. Holland,, and P. Ahlquist (ed.), RNA Genetics, vol. 2. CRC Press Inc., Boca Raton, Fla.

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