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. 1991 Jun;65(6):2960–2967. doi: 10.1128/jvi.65.6.2960-2967.1991

Quantitation of relative fitness and great adaptability of clonal populations of RNA viruses.

J J Holland 1, J C de la Torre 1, D K Clarke 1, E Duarte 1
PMCID: PMC240937  PMID: 2033662

Abstract

We describe a sensitive, internally controlled method for comparing the genetic adaptability and relative fitness of virus populations in constant or changing host environments. Certain monoclonal antibody-resistant mutants of vesicular stomatitis virus can compete equally during serial passages in mixtures with the parental wild-type clone from which they were derived. These genetically marked "surrogate wild-type" neutral mutants, when mixed with wild-type virus, allow reliable measurement of changes in virus fitness and of virus adaptation to different host environments. Quantitative fitness vector plots demonstrate graphically that even clones of an RNA virus are composed of complex variant populations (quasispecies). Variants of greater fitness (competitive replication ability) were selected within very few passages of virus clones in new host cells or animals. Even clones which were well adapted to BHK21 cells gained further fitness during repeated passages in BHK21 cells.

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Selected References

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  1. Air G. M., Gibbs A. J., Laver W. G., Webster R. G. Evolutionary changes in influenza B are not primarily governed by antibody selection. Proc Natl Acad Sci U S A. 1990 May;87(10):3884–3888. doi: 10.1073/pnas.87.10.3884. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Batschelet E., Domingo E., Weissmann C. The proportion of revertant and mutant phage in a growing population, as a function of mutation and growth rate. Gene. 1976;1(1):27–32. doi: 10.1016/0378-1119(76)90004-4. [DOI] [PubMed] [Google Scholar]
  3. Bilsel P. A., Nichol S. T. Polymerase errors accumulating during natural evolution of the glycoprotein gene of vesicular stomatitis virus Indiana serotype isolates. J Virol. 1990 Oct;64(10):4873–4883. doi: 10.1128/jvi.64.10.4873-4883.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cattaneo R., Schmid A., Eschle D., Baczko K., ter Meulen V., Billeter M. A. Biased hypermutation and other genetic changes in defective measles viruses in human brain infections. Cell. 1988 Oct 21;55(2):255–265. doi: 10.1016/0092-8674(88)90048-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cohen J. I., Rosenblum B., Ticehurst J. R., Daemer R. J., Feinstone S. M., Purcell R. H. Complete nucleotide sequence of an attenuated hepatitis A virus: comparison with wild-type virus. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2497–2501. doi: 10.1073/pnas.84.8.2497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. DePolo N. J., Giachetti C., Holland J. J. Continuing coevolution of virus and defective interfering particles and of viral genome sequences during undiluted passages: virus mutants exhibiting nearly complete resistance to formerly dominant defective interfering particles. J Virol. 1987 Feb;61(2):454–464. doi: 10.1128/jvi.61.2.454-464.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Domingo E., Dávila M., Ortín J. Nucleotide sequence heterogeneity of the RNA from a natural population of foot-and-mouth-disease virus. Gene. 1980 Nov;11(3-4):333–346. doi: 10.1016/0378-1119(80)90073-6. [DOI] [PubMed] [Google Scholar]
  8. Domingo E., Flavell R. A., Weissmann C. In vitro site-directed mutagenesis: generation and properties of an infectious extracistronic mutant of bacteriophage Qbeta. Gene. 1976;1(1):3–25. doi: 10.1016/0378-1119(76)90003-2. [DOI] [PubMed] [Google Scholar]
  9. Domingo E., Martínez-Salas E., Sobrino F., de la Torre J. C., Portela A., Ortín J., López-Galindez C., Pérez-Breña P., Villanueva N., Nájera R. The quasispecies (extremely heterogeneous) nature of viral RNA genome populations: biological relevance--a review. Gene. 1985;40(1):1–8. doi: 10.1016/0378-1119(85)90017-4. [DOI] [PubMed] [Google Scholar]
  10. Domingo E., Sabo D., Taniguchi T., Weissmann C. Nucleotide sequence heterogeneity of an RNA phage population. Cell. 1978 Apr;13(4):735–744. doi: 10.1016/0092-8674(78)90223-4. [DOI] [PubMed] [Google Scholar]
  11. Durbin R. K., Stollar V. Sequence analysis of the E2 gene of a hyperglycosylated, host restricted mutant of Sindbis virus and estimation of mutation rate from frequency of revertants. Virology. 1986 Oct 15;154(1):135–143. doi: 10.1016/0042-6822(86)90436-8. [DOI] [PubMed] [Google Scholar]
  12. ENDERS J. F., KATZ S. L., MILOVANOVIC M. V., HOLLOWAY A. Studies on an attenuated measles-virus vaccine. I. Development and preparations of the vaccine: technics for assay of effects of vaccination. N Engl J Med. 1960 Jul 28;263:153–159. doi: 10.1056/NEJM196007282630401. [DOI] [PubMed] [Google Scholar]
  13. Fields B. N., Joklik W. K. Isolation and preliminary genetic and biochemical characterization of temperature-sensitive mutants of reovirus. Virology. 1969 Mar;37(3):335–342. doi: 10.1016/0042-6822(69)90217-7. [DOI] [PubMed] [Google Scholar]
  14. Fisher A. G., Ensoli B., Looney D., Rose A., Gallo R. C., Saag M. S., Shaw G. M., Hahn B. H., Wong-Staal F. Biologically diverse molecular variants within a single HIV-1 isolate. Nature. 1988 Aug 4;334(6181):444–447. doi: 10.1038/334444a0. [DOI] [PubMed] [Google Scholar]
  15. Gebauer F., de la Torre J. C., Gomes I., Mateu M. G., Barahona H., Tiraboschi B., Bergmann I., de Mello P. A., Domingo E. Rapid selection of genetic and antigenic variants of foot-and-mouth disease virus during persistence in cattle. J Virol. 1988 Jun;62(6):2041–2049. doi: 10.1128/jvi.62.6.2041-2049.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gojobori T., Yokoyama S. Rates of evolution of the retroviral oncogene of Moloney murine sarcoma virus and of its cellular homologues. Proc Natl Acad Sci U S A. 1985 Jun;82(12):4198–4201. doi: 10.1073/pnas.82.12.4198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hahn B. H., Shaw G. M., Taylor M. E., Redfield R. R., Markham P. D., Salahuddin S. Z., Wong-Staal F., Gallo R. C., Parks E. S., Parks W. P. Genetic variation in HTLV-III/LAV over time in patients with AIDS or at risk for AIDS. Science. 1986 Jun 20;232(4757):1548–1553. doi: 10.1126/science.3012778. [DOI] [PubMed] [Google Scholar]
  18. Hahn C. S., Rice C. M., Strauss E. G., Lenches E. M., Strauss J. H. Sindbis virus ts103 has a mutation in glycoprotein E2 that leads to defective assembly of virions. J Virol. 1989 Aug;63(8):3459–3465. doi: 10.1128/jvi.63.8.3459-3465.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Holland J. J., Domingo E., de la Torre J. C., Steinhauer D. A. Mutation frequencies at defined single codon sites in vesicular stomatitis virus and poliovirus can be increased only slightly by chemical mutagenesis. J Virol. 1990 Aug;64(8):3960–3962. doi: 10.1128/jvi.64.8.3960-3962.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Holland J. J., Grabau E. A., Jones C. L., Semler B. L. Evolution of multiple genome mutations during long-term persistent infection by vesicular stomatitis virus. Cell. 1979 Mar;16(3):495–504. doi: 10.1016/0092-8674(79)90024-2. [DOI] [PubMed] [Google Scholar]
  21. Holland J. J., de la Torre J. C., Steinhauer D. A., Clarke D., Duarte E., Domingo E. Virus mutation frequencies can be greatly underestimated by monoclonal antibody neutralization of virions. J Virol. 1989 Dec;63(12):5030–5036. doi: 10.1128/jvi.63.12.5030-5036.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Holland J., Spindler K., Horodyski F., Grabau E., Nichol S., VandePol S. Rapid evolution of RNA genomes. Science. 1982 Mar 26;215(4540):1577–1585. doi: 10.1126/science.7041255. [DOI] [PubMed] [Google Scholar]
  23. Huovilainen A., Hovi T., Kinnunen L., Takkinen K., Ferguson M., Minor P. Evolution of poliovirus during an outbreak: sequential type 3 poliovirus isolates from several persons show shifts of neutralization determinants. J Gen Virol. 1987 May;68(Pt 5):1373–1378. doi: 10.1099/0022-1317-68-5-1373. [DOI] [PubMed] [Google Scholar]
  24. Jansen R. W., Newbold J. E., Lemon S. M. Complete nucleotide sequence of a cell culture-adapted variant of hepatitis A virus: comparison with wild-type virus with restricted capacity for in vitro replication. Virology. 1988 Apr;163(2):299–307. doi: 10.1016/0042-6822(88)90270-x. [DOI] [PubMed] [Google Scholar]
  25. Kew O. M., Nottay B. K., Hatch M. H., Nakano J. H., Obijeski J. F. Multiple genetic changes can occur in the oral poliovaccines upon replication in humans. J Gen Virol. 1981 Oct;56(Pt 2):337–347. doi: 10.1099/0022-1317-56-2-337. [DOI] [PubMed] [Google Scholar]
  26. Kinnunen L., Huovilainen A., Pöyry T., Hovi T. Rapid molecular evolution of wild type 3 poliovirus during infection in individual hosts. J Gen Virol. 1990 Feb;71(Pt 2):317–324. doi: 10.1099/0022-1317-71-2-317. [DOI] [PubMed] [Google Scholar]
  27. Lande R. Expected time for random genetic drift of a population between stable phenotypic states. Proc Natl Acad Sci U S A. 1985 Nov;82(22):7641–7645. doi: 10.1073/pnas.82.22.7641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Lefrancios L., Lyles D. S. The interactionof antiody with the major surface glycoprotein of vesicular stomatitis virus. I. Analysis of neutralizing epitopes with monoclonal antibodies. Virology. 1982 Aug;121(1):157–167. [PubMed] [Google Scholar]
  29. Lefrancois L., Lyles D. S. Antigenic determinants of vesicular stomatitis virus: analysis with antigenic variants. J Immunol. 1983 Jan;130(1):394–398. [PubMed] [Google Scholar]
  30. Lefrancois L., Lyles D. S. The interaction of antibody with the major surface glycoprotein of vesicular stomatitis virus. II. Monoclonal antibodies of nonneutralizing and cross-reactive epitopes of Indiana and New Jersey serotypes. Virology. 1982 Aug;121(1):168–174. doi: 10.1016/0042-6822(82)90126-x. [DOI] [PubMed] [Google Scholar]
  31. Minor P. D., John A., Ferguson M., Icenogle J. P. Antigenic and molecular evolution of the vaccine strain of type 3 poliovirus during the period of excretion by a primary vaccinee. J Gen Virol. 1986 Apr;67(Pt 4):693–706. doi: 10.1099/0022-1317-67-4-693. [DOI] [PubMed] [Google Scholar]
  32. Moss E. G., O'Neill R. E., Racaniello V. R. Mapping of attenuating sequences of an avirulent poliovirus type 2 strain. J Virol. 1989 May;63(5):1884–1890. doi: 10.1128/jvi.63.5.1884-1890.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Mudd J. A., Summers D. F. Protein synthesis in vesicular stomatitis virus-infected HeLa cells. Virology. 1970 Oct;42(2):328–340. doi: 10.1016/0042-6822(70)90277-1. [DOI] [PubMed] [Google Scholar]
  34. Nichol S. T. Genetic diversity of enzootic isolates of vesicular stomatitis virus New Jersey. J Virol. 1988 Feb;62(2):572–579. doi: 10.1128/jvi.62.2.572-579.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Nichol S. T., Rowe J. E., Fitch W. M. Glycoprotein evolution of vesicular stomatitis virus New Jersey. Virology. 1989 Feb;168(2):281–291. doi: 10.1016/0042-6822(89)90268-7. [DOI] [PubMed] [Google Scholar]
  36. O'Hara P. J., Horodyski F. M., Nichol S. T., Holland J. J. Vesicular stomatitis virus mutants resistant to defective-interfering particles accumulate stable 5'-terminal and fewer 3'-terminal mutations in a stepwise manner. J Virol. 1984 Mar;49(3):793–798. doi: 10.1128/jvi.49.3.793-798.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Omata T., Kohara M., Kuge S., Komatsu T., Abe S., Semler B. L., Kameda A., Itoh H., Arita M., Wimmer E. Genetic analysis of the attenuation phenotype of poliovirus type 1. J Virol. 1986 May;58(2):348–358. doi: 10.1128/jvi.58.2.348-358.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Parvin J. D., Moscona A., Pan W. T., Leider J. M., Palese P. Measurement of the mutation rates of animal viruses: influenza A virus and poliovirus type 1. J Virol. 1986 Aug;59(2):377–383. doi: 10.1128/jvi.59.2.377-383.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Pilipenko E. V., Blinov V. M., Romanova L. I., Sinyakov A. N., Maslova S. V., Agol V. I. Conserved structural domains in the 5'-untranslated region of picornaviral genomes: an analysis of the segment controlling translation and neurovirulence. Virology. 1989 Feb;168(2):201–209. doi: 10.1016/0042-6822(89)90259-6. [DOI] [PubMed] [Google Scholar]
  40. Pincus S. E., Diamond D. C., Emini E. A., Wimmer E. Guanidine-selected mutants of poliovirus: mapping of point mutations to polypeptide 2C. J Virol. 1986 Feb;57(2):638–646. doi: 10.1128/jvi.57.2.638-646.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Portner A., Webster R. G., Bean W. J. Similar frequencies of antigenic variants in Sendai, vesicular stomatitis, and influenza A viruses. Virology. 1980 Jul 15;104(1):235–238. doi: 10.1016/0042-6822(80)90382-7. [DOI] [PubMed] [Google Scholar]
  42. Preston B. D., Poiesz B. J., Loeb L. A. Fidelity of HIV-1 reverse transcriptase. Science. 1988 Nov 25;242(4882):1168–1171. doi: 10.1126/science.2460924. [DOI] [PubMed] [Google Scholar]
  43. Pringle C. R. Genetic characteristics of conditional lethal mutants of vesicular stomatitis virus induced by 5-fluorouracil, 5-azacytidine, and ethyl methane sulfonate. J Virol. 1970 May;5(5):559–567. doi: 10.1128/jvi.5.5.559-567.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Roberts J. D., Bebenek K., Kunkel T. A. The accuracy of reverse transcriptase from HIV-1. Science. 1988 Nov 25;242(4882):1171–1173. doi: 10.1126/science.2460925. [DOI] [PubMed] [Google Scholar]
  45. Sedivy J. M., Capone J. P., RajBhandary U. L., Sharp P. A. An inducible mammalian amber suppressor: propagation of a poliovirus mutant. Cell. 1987 Jul 31;50(3):379–389. doi: 10.1016/0092-8674(87)90492-2. [DOI] [PubMed] [Google Scholar]
  46. Smith D. B., Inglis S. C. The mutation rate and variability of eukaryotic viruses: an analytical review. J Gen Virol. 1987 Nov;68(Pt 11):2729–2740. doi: 10.1099/0022-1317-68-11-2729. [DOI] [PubMed] [Google Scholar]
  47. Sobrino F., Dávila M., Ortín J., Domingo E. Multiple genetic variants arise in the course of replication of foot-and-mouth disease virus in cell culture. Virology. 1983 Jul 30;128(2):310–318. doi: 10.1016/0042-6822(83)90258-1. [DOI] [PubMed] [Google Scholar]
  48. Spindler K. R., Horodyski F. M., Holland J. J. High multiplicities of infection favor rapid and random evolution of vesicular stomatitis virus. Virology. 1982 May;119(1):96–108. doi: 10.1016/0042-6822(82)90068-x. [DOI] [PubMed] [Google Scholar]
  49. Steinhauer D. A., Holland J. J. Rapid evolution of RNA viruses. Annu Rev Microbiol. 1987;41:409–433. doi: 10.1146/annurev.mi.41.100187.002205. [DOI] [PubMed] [Google Scholar]
  50. Steinhauer D. A., de la Torre J. C., Holland J. J. High nucleotide substitution error frequencies in clonal pools of vesicular stomatitis virus. J Virol. 1989 May;63(5):2063–2071. doi: 10.1128/jvi.63.5.2063-2071.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Steinhauer D. A., de la Torre J. C., Meier E., Holland J. J. Extreme heterogeneity in populations of vesicular stomatitis virus. J Virol. 1989 May;63(5):2072–2080. doi: 10.1128/jvi.63.5.2072-2080.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Strauss J. H., Strauss E. G. Evolution of RNA viruses. Annu Rev Microbiol. 1988;42:657–683. doi: 10.1146/annurev.mi.42.100188.003301. [DOI] [PubMed] [Google Scholar]
  53. Valcárcel J., Ortín J. Phenotypic hiding: the carryover of mutations in RNA viruses as shown by detection of mar mutants in influenza virus. J Virol. 1989 Sep;63(9):4107–4109. doi: 10.1128/jvi.63.9.4107-4109.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Vandepol S. B., Lefrancois L., Holland J. J. Sequences of the major antibody binding epitopes of the Indiana serotype of vesicular stomatitis virus. Virology. 1986 Jan 30;148(2):312–325. doi: 10.1016/0042-6822(86)90328-4. [DOI] [PubMed] [Google Scholar]
  55. Ward C. D., Stokes M. A., Flanegan J. B. Direct measurement of the poliovirus RNA polymerase error frequency in vitro. J Virol. 1988 Feb;62(2):558–562. doi: 10.1128/jvi.62.2.558-562.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Westrop G. D., Wareham K. A., Evans D. M., Dunn G., Minor P. D., Magrath D. I., Taffs F., Marsden S., Skinner M. A., Schild G. C. Genetic basis of attenuation of the Sabin type 3 oral poliovirus vaccine. J Virol. 1989 Mar;63(3):1338–1344. doi: 10.1128/jvi.63.3.1338-1344.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Wilusz J., Youngner J. S., Keene J. D. Base mutations in the terminal noncoding regions of the genome of vesicular stomatitis virus isolated from persistent infections of L cells. Virology. 1985 Jan 30;140(2):249–256. doi: 10.1016/0042-6822(85)90363-0. [DOI] [PubMed] [Google Scholar]
  58. de la Torre J. C., Wimmer E., Holland J. J. Very high frequency of reversion to guanidine resistance in clonal pools of guanidine-dependent type 1 poliovirus. J Virol. 1990 Feb;64(2):664–671. doi: 10.1128/jvi.64.2.664-671.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]

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