Variation in Influenza Virus Genes

Epidemiological, Pathogenic, and Evolutionary Consequences
  • Frances I. Smith
  • Peter Palese
Part of the The Viruses book series (VIRS)


Influenza viruses can be classified into three types: A, B, and C. Strains of the same type share serologically cross-reactive matrix (M) proteins and nucleoproteins (NP), which are the major components of the virus. Recent technological advances have resulted in the cloning and sequencing of genes of many members of each type. The results indicate that the genetic information of influenza viruses is not static and that the amount and pattern of variation differs for the three types of influenza virus. The purpose of this chapter is to review the variation seen within the different types, with an emphasis on human influenza viruses. Also, we consider factors that may contribute to this variation and attempt to correlate the differences seen among the three types with differences in the biological properties and epidemiology of these viruses Finally, an attempt is made to compare variation of influenza viruses with that seen in other RNA viruses.


Influenza Virus Human Influenza Equine Infectious Anemia Virus Live Attenuate Influenza Vaccine Human Influenza Virus 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Air, G. M., and Compans, R. W., 1983, Influenza B and influenza C viruses, in: Genetics of Influenza Viruses ( P. Palese and D. W. Kingsbury, eds.), pp. 280–304, Springer-Verlag, New York.Google Scholar
  2. Akoto-Amanfu, E., Sivasubramanian, N., and Nayak, D. P., 1987, Primary structure of the polymerase acidic (PA) gene of influenza b virus (B/Sing/22/79, Virology 159: 147–153.PubMedCrossRefGoogle Scholar
  3. Askonas, B. A., McMichael, A. J., and Webster, R. G., 1982, The immune response to influenza viruses and the problem of protection against infection, in: Basic and Applied Research ( A. S. Beare, ed.), pp. 157–188, CRC Press, Boca Raton, Florida.Google Scholar
  4. Baez, M., Palese, P., and Kilbourne, E. D., 1980, Gene composition of high-yielding influenza vaccine strains obtained by recombination, J. Infect. Dis. 141: 362–369.PubMedCrossRefGoogle Scholar
  5. Bao-lan, L., Webster, R. G., Brown, L. E., and Nerome, K., 1983, Heterogeneity of influenza B viruses, Bull. WHO 61: 681–687.PubMedGoogle Scholar
  6. Bean, W. J., Cox, N. J., and Kendal, A. P., 1980, Recombination of human influenza A viruses in nature, Nature (Lond.) 284: 638–640.CrossRefGoogle Scholar
  7. Bean, W. J., Kawaoka, Y., Wood, J. M., Pearson, J. E., and Webster, R. G., 1985, Characterization of virulent and avirulent A/chicken/Pennsylvania/83 influenza A viruses: Potential role of defective interfering RNAs in nature, J. Virol. 54: 151–160.PubMedGoogle Scholar
  8. Bean, W. J., and Webster, R. G., 1978, Phenotype properties associated with influenza genome segments, in: Negative Strand Viruses and the Host Cell ( B. W. J. Mahy and R. D. Barry, eds.), pp. 685–692, Academic, Orlando, Florida.Google Scholar
  9. Beklemishev, A. B., Blynov, V. M., Vassilen, S. K., Golovin, S. Y., Karginov, V A, Mamayev, L. V., Netesov, S. V., Petrov, N. A., and Safronov, P. F., 1986, Nucleotide sequence of a full-length DNA copy of the influenza virus A-Kiev-59–79 (H1N1)-type nucleoprotein gene, Bioorg. Khim. 12: 369–374.PubMedGoogle Scholar
  10. Berton, M. T., Naeve, C. W., and Webster, R. G., 1984, Antigenic structure of the influenza B virus hemagglutinin: Nucleotide sequence analysis of antigenic variants selected with monoclonal antibodies, J. Virol. 52: 919–927.PubMedGoogle Scholar
  11. Bishop, D. H. L., Huddleston, J. A., and Brownlee, G. G., 1982a, The complete sequence of RNA segment 2 of influenza A/NT/60/68 and its encoded P1 protein, Nucl. Acids Res. 10: 1335–1343.PubMedCrossRefGoogle Scholar
  12. Bishop, D. H. L., Jones, K. L., Huddleston, J. A., and Brownlee, G. G., 1982b, Influenza A virus evolution: Complete sequences of influenza A/NT/60/68 RNA segment 3 and its predicted acidic P polypeptide compared with those of influenza A/PR/8/34, Virology 120: 481–489.PubMedCrossRefGoogle Scholar
  13. Blok, J., and Air, G. M., 1980, Comparative nucleotide sequences at the 3’ end of the neuraminidase gene from eleven influenza type A viruses, Virology 107: 50–60.PubMedCrossRefGoogle Scholar
  14. Blok, J., and Air, G. M., 1982a, Sequence variation at the 3’ end of the neuraminidase gene from 39 influenza type A viruses. Virology 121:211–229.CrossRefGoogle Scholar
  15. Blok, J., and Air, G. M., 1982b, Block deletions in the neuraminidase genes from some influenza A viruses of the NI subtype, Virology 118: 229–234.PubMedCrossRefGoogle Scholar
  16. Bosch, F. X., Garten, W., Klenk, H.-D., and Rott, R., 1981, Proteolytic cleavage of influenza virus hemagglutinins: Primary structure of the connecting peptide between HAl and HA2 determines proteolytic cleavability and pathogenicity of avian influenza viruses, Virology 113:725–735.PubMedCrossRefGoogle Scholar
  17. Both, G. W., and Sleigh, M. J., 1981, Conservation and variation in the hemagglutinins of Hong Kong subtype influenza viruses during antigenic drift, J. Virol. 39: 663–672.PubMedGoogle Scholar
  18. Both, G. W., Sleigh, M. J., Cox, N. J., and Kendal, A. P., 1983, Antigenic drift in influenza virus H3 hemagglutinin from 1968–1980: Multiple evolutionary pathways and sequential amino acid changes at key antigenic sites, J. Virol. 48: 52–60.PubMedGoogle Scholar
  19. Brand, C., and Palese, P., 1980, Sequential passage of influenza virus in embryonated eggs or tissue culture: Emergence of mutants, Virology 107: 424–433.PubMedCrossRefGoogle Scholar
  20. Briedis, D. J., and Lamb, R. A., 1982, The influenza B virus RNA segment 8 codes for two nonstructural proteins, J. Virol. 42: 186–193.PubMedGoogle Scholar
  21. Briedis, D. J., and Tobin, M., 1984, Influenza B virus genome: Complete nucleotide sequence of the influenza B/Lee/40 virus genome RNA segment 5 encoding the nucleoprotein and comparison with the B/Singapore/222/79 nucleoprotein, Virology 133: 448–455.PubMedCrossRefGoogle Scholar
  22. Briedis, D. J., Lamb, R. A., and Choppin, P. W., 1982, Sequence of RNA segment of the influenza B virus genome: Partial amino acid homology between the membrane proteins (M1) of influenza A and B viruses and conservation of a second open reading frame, Virology 116: 581–588.PubMedCrossRefGoogle Scholar
  23. Buckler-White, A. J., and Murphy, B. R., 1986, Nucleotide sequence analysis of the nucleoprotein gene of an avian and a human influenza virus strain identifies two classes of nucleoproteins, Virology 155: 345–355.PubMedCrossRefGoogle Scholar
  24. Buckler-White, A. J., Naeve, C. W., and Murphy, B. R., 1986, Characterization of a gene coding for M proteins which is involved in host range restriction of an avian influenza A virus in monkeys, J. Virol. 57: 697–700.PubMedGoogle Scholar
  25. Buonagurio, D. A., Krystal, M., Palese, P., DeBorde, D. C., and Maassab, H. F., 1984, Analysis of an influenza A virus mutant with a deletion in the NS segment, J. Virol. 49: 418–425.PubMedGoogle Scholar
  26. Buonagurio, D. A., Nakada, S., Desselberger, U., Krystal, M., and Palese, P., 1985, Noncumulative sequence changes in the hemagglutinin genes of influenza C virus isolates, Virology 146: 221–232.PubMedCrossRefGoogle Scholar
  27. Buonagurio, D. A., Nakada, S., Fitch, W. M., and Palese, P., 1986a, Epidemiology of influenza C virus in man: Multiple evolutionary lineages and low rate of change, Virology 153: 12–21.PubMedCrossRefGoogle Scholar
  28. Buonagurio, D. A., Nakada, S., Parvin, J. D., Krystal, M., Palese, P., and Fitch, W. M., 1986b, Evolution of human influenza A viruses over 50 years: Rapid, uniform rate of change in NS gene. Science 232: 980–982.PubMedCrossRefGoogle Scholar
  29. Chakraverty, P., 1978, Antigenic relationship between influenza C viruses, Arch. Virol. 58: 341–348.PubMedCrossRefGoogle Scholar
  30. Coffin, J. M., Tsichlis, P. N., Barker, C. S., and Voynow, S., 1980, Variation in avian retro-virus genomes, Ann. NY Acad. Sci. 354: 410–425.PubMedCrossRefGoogle Scholar
  31. Colman, P. M., and Ward, C. W., 1985, Structure and diversity of influenza virus neuraminidase, Curr. Topics Microbiol. Immunol. 114: 177–255.CrossRefGoogle Scholar
  32. Colman, P. M., Varghese, J. N., and Laver, W. G., 1983, Structure of the catalytic and antigenic sites in influenza virus neuraminidase, Nature (Lond.) 303: 41–44.CrossRefGoogle Scholar
  33. Concannon, P., Cummings, I. W., and Salser, W. A., 1984, Nucleotide sequence of the influenza virus A/USSR/90/77 hemagglutinin gene, J. Virol. 49: 276–278.PubMedGoogle Scholar
  34. Corey, L., Rubin, R. J., Hattwick, M. A. W., Noble, G. R., and Cassidy, E., 1976, A nationwide outbreak of Reye’s syndrome: Its epidemiologic relationship to influenza B, Am. J. Med. 61: 615–625.PubMedCrossRefGoogle Scholar
  35. Cox, N. J., 1986, Progress and limitations in understanding the genetic basis for attenuation of live attenuated influenza vaccines, in: Options for the Control of Influenza ( A. P. Kendal and P. A. Patriarca, eds.), pp. 207–221, Liss, New York.Google Scholar
  36. Cox, N. J., Bai, Z. S., and Kendal, A. P., 1983, Laboratory-based surveillance of influenza A (H1N1) and A (H3N2) viruses in 1980–81: Antigenic and genomic analyses, Bull. WHO 61: 143–152.PubMedGoogle Scholar
  37. Daniels, R. S., Downie, J. C., Hay, M., Knossow, M., Skehel, J. J., Wang, M. L., and Wiley, D. C., 1985, Fusion mutants of the influenza virus hemagglutinin glycoprotein, Cell 40: 431–439.PubMedCrossRefGoogle Scholar
  38. de Borde, D. C., Donabedian, A. M., Herlocher, M. L., Naeve, C. W., and Maassab, H. F., 1988, Sequence comparison of wild type and cold-adapted B/Ann Arbor/1/66 influenza virus genes, Virology 163: 429–443.CrossRefGoogle Scholar
  39. de la Torre, J. C., Martinez-Salas, E., Diez, J., Villaverde, A., Gebaver, F., Rocha, E., Davila, M., and Domingo, E., 1988, Coevolution of cells and viruses in a persistent infection of foot and mouth disease virus in cell culture, J. Virol. 62: 2050–2058.PubMedGoogle Scholar
  40. Deom, C. M., Caton, A. J., and Schultze, I. T., 1986. Host cell-mediated selection of a mutant influenza A virus that has lost a complex oligosaccharide from the tip of the hemagglutinin, Proc. Natl. Acad. Sci. USA 83: 3771–3775.PubMedCrossRefGoogle Scholar
  41. Deshpande, K. L., Fried, V. A., Ando, M., and Webster, R. G., 1987, Glycosylation affects cleavage of an H5N2 influenza virus hemagglutinin and regulates virulence, Proc. Natl. Acad. Sci. USA 84: 36–40.PubMedCrossRefGoogle Scholar
  42. Deshpande, K. L., Naeve, C. L., and Webster, R. G., 1985, The neuraminidase of the virulent and avirulent A/chicken/Pennsylvania/83 (H5N2) influenza A viruses: Sequence and antigenic analysis, Virology 147: 49–60.PubMedCrossRefGoogle Scholar
  43. Desselberger, U., Nakajima, K., Alfino, P., Pedersen, F. S., Haseltine, W. A., Hannoun, C., and Palese, P., 1978, Biochemical evidence that “new” influenza virus strains in nature may arise by recombination (reassortment), Proc. Natl. Acad. Sci. USA 75: 3341–3345.PubMedCrossRefGoogle Scholar
  44. Domingo, E., Sabo, D., Taniguchi, T., and Weissmann, C., 1978, Nucleotide sequence heterogeneity of an RNA phage population, Cell 13: 735–744.PubMedCrossRefGoogle Scholar
  45. Doms, R. W., Gething, M. -J., Henneberry, J., White, J., and Helenius, A., 1986, Variant influenza virus hemagglutinin that induces fusion at elevated pH, J. Viral. 57: 603–613.Google Scholar
  46. Dougherty, J. P., and Temin, H. M., 1988, Determination of the rate of base-pair substitution and insertion mutations in retrovirus replication, J. Virol. 62: 2817–2822.PubMedGoogle Scholar
  47. Durbin, R. K., and Stollar, V., 1986, 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 154: 135–143.PubMedCrossRefGoogle Scholar
  48. Emini, E. A., Kao, S.-Y., Lewis, A. J., Crainic, R., and Wimmer, E., 1983, Functional basis of poliovirus neutralization determined with monospecific neutralizing antibodies, J. Virol. 46: 466–474.PubMedGoogle Scholar
  49. Fang, R., Min Jou, W., Huylebroeck, D., Devos, R., and Fiers, W., 1981, Complete structure of A/Duck/Ukraine/63 influenza hemagglutinin gene• Animal virus as progenitor of human H3 Hong Kong 1968 influenza hemagglutinin, Cell 25: 315–323.PubMedCrossRefGoogle Scholar
  50. Fields, S., and Winter, G., 1982, Nucleotide sequences of influenza virus segments 1 and 3 reveal mosaic structure of a small viral RNA segment, Cell 28: 303–313.PubMedCrossRefGoogle Scholar
  51. Fields, S., Winter, G., and Brownlee, G. G., 1981, Structure of the neuraminidase gene in human influenza virus A/PR/8/34, Nature (Land.) 290: 213–217.CrossRefGoogle Scholar
  52. Fitch, W. M., 1971, Toward defining the course of evolution. Minimum change for a specific tree topology, Syst. Zool. 20: 406–416.CrossRefGoogle Scholar
  53. Gething, M.-J., Bye, J., Skehel, J. J., and Waterfield, M. D., 1980, Cloning and DNA sequence of double-stranded copies of hemagglutinin genes from H2 and H3 strains elucidates antigenic shift and drift in human influenza virus, Nature (Lond.) 287: 301–306.CrossRefGoogle Scholar
  54. Giesendorf, B., Bosch, F. X., Orlich, M., Scholtissek, C., and Rott, R., 1986, Studies on the temperature sensitivity of influenza A virus reassortants nonpathogenic for chicken, Virus Res. 5: 27–42.PubMedCrossRefGoogle Scholar
  55. Guo, Y. J., and Desselberger, U., 1984, Genome analysis of influenza C viruses isolated in 1981/1982 from pigs in China, J. Gen. Virol. 65: 1857–1872.CrossRefGoogle Scholar
  56. Guo, Y. J., Jin, F. G., Wang, P., Wang, M., and Zhu, J. M., 1983, Isolation of influenza C virus from pigs and experimental infection of pigs with influenza C virus, j. Gen. Virol. 64: 177–182.PubMedCrossRefGoogle Scholar
  57. Haase, A., 1986, Pathogenesis of lentivirus infections, Nature (Lond.) 322:130–136.Google Scholar
  58. 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., and Parks, W. P., 1986, Genetic variation in HTLVIII/LAV over time in patients with AIDS or at risk for AIDS, Science 232: 1548–1553.PubMedCrossRefGoogle Scholar
  59. Hall, R. M., and Air, G. M., 1981, Variation in nucleotide sequences coding for the N-terminal regions of the matrix and nonstructural proteins of influenza A viruses, Virology 38: 1–7.Google Scholar
  60. Haller, 0., 1981, Inborn resistance of mice to orthomyxoviruses, Curr. Top. Microbiol. Immunol. 92: 25–52.CrossRefGoogle Scholar
  61. Hauptmann, R., Clarke, L. D., Mountford, R. C., Bachmayer, H., and Almond, J. W., 1983, Nucleotide sequence of the haemagglutinin gene of influenza virus A/England/321/77, J. Gen. Virol. 64: 215–220.PubMedCrossRefGoogle Scholar
  62. Hay, A. J., Wolstenholme, A. J., Skehel, J. J., and Smith, M. H., 1985, The molecular basis of the specific anti-influenza action of amantadine, EMBO J. 4: 3021–3024.PubMedGoogle Scholar
  63. Hay, A. J., Wolstenholme, A. J., Zambon, M. C., Skehel, J. J., Smith, M. H., and Wharton, S. A., 1987, The molecular basis of the anti-influenza A action of amantadine and identification of a role for the M2 protein in influenza virus replication, in: The Biology of Negative Strand Viruses ( B. Mahy and D. Kolakofsky, eds.), pp. 18–25, Elsevier, Amsterdam.Google Scholar
  64. Herrler, G., Durkop, I., Becht, H., and Klenk, H.-D., 1988, The glycoprotein of influenza C virus is the hemagglutinin, esterase and fusion factor, J. Gen. Virol. 69: 839–846.PubMedCrossRefGoogle Scholar
  65. Herder, G., Rott, R., Klenk, H.-D., Muller, H.-P., Shukla, A. K., and Schauer, R., 1985, The receptor-destroying enzyme of influenza C virus is neuraminate-O-acetylesterase, EMBO J. 4: 1503–1506.Google Scholar
  66. Hinshaw, V. S., Bean, W. J., Jr., Webster, R. G., and Easterday, B. C., 1978, The prevalence of influenza viruses in swine and the antigenic and genetic relatedness of influenza viruses from man and swine, Virology 84: 51–62.PubMedCrossRefGoogle Scholar
  67. Hinshaw, V. S., Bean, W. J., Webster, R. G., and Sriram, G., 1980, Genetic reassortment ofGoogle Scholar
  68. influenza A viruses in the intestinal tract of ducks, Virology 102:412–419.Google Scholar
  69. Hiti, A. L., and Nayak, D. P., 1982, Complete nucleotide sequence of the neuraminidaseGoogle Scholar
  70. gene of human influenza virus A/WSN/33, J. Virol. 41: 730–734.Google Scholar
  71. Hiti, A. R., David, A. R., and Nayak, D. P., 1981, Complete sequence analysis shows that the hemagglutinins of the HO and H2 subtypes of human influenza virus are closely related, Virology 111: 113–124.PubMedCrossRefGoogle Scholar
  72. Holland, J., Spindler, K., Horodyski, F., Grabau, E., Nichol, S., and VandePol, S., 1982, Rapid evolution of RNA genomes, Science 215: 1577–1585.PubMedCrossRefGoogle Scholar
  73. Hovanec, D. L., and Air, G. M., 1984, Antigenic structure of the hemagglutinin of influenza virus B/Hong Kong/8/73 as determined from gene sequence analysis of variants selected with monoclonal antibodies, Virology 139: 384–392.PubMedCrossRefGoogle Scholar
  74. Huddleston, J. A., and Brownlee, G. G., 1982, The sequence of the nucleoprotein gene of human influenza A virus strain A/NT/60/68, Nucl. Acids Res. 10: 1029–1038.PubMedCrossRefGoogle Scholar
  75. Hurwitz, E. S., Nelson, D. B., Davis, C., Morens, D., and Schonberger, L. B., 1982, National surveillance for Reye’s syndrome: A five year review, Pediatrics 70: 895–900.PubMedGoogle Scholar
  76. Jones, K. L., Huddleston, J. A., and Brownlee, G. G., 1983, The sequence of RNA segment 1 of influenza virus A/NT/60/68 and its comparison with the corresponding segment of strains A/PR/8/34 and A/WSN/33, Nucl. Acids Res. 11: 1555–1566.PubMedCrossRefGoogle Scholar
  77. Kaptein, J. S., and Nayak, D. P., 1982, Complete nucleotide sequence of the polymerase 3 gene of human influenza virus A/WSN/33, J. Virol. 42: 55–63.PubMedGoogle Scholar
  78. Katagiri, S., Ohizumi, A., and Homma, M., 1983, An outbreak of type C influenza in a children’s home, J. Infect. Dis. 148: 51–56.PubMedCrossRefGoogle Scholar
  79. Kawamura, H., Tashiro, M., Kitame, F., Homma, M., and Nakamura, K., 1986, Genetic variation among human strains of influenza C virus isolated in Japan, Virus Res. 4: 275288.Google Scholar
  80. Kemdirim, S., Palefsky, J., and Briedis, D. J., 1986, Influenza B virus PB1 protein: Nucleotide sequence of the genome RNA segment predicts a high degree of structural homology with the corresponding influenza A virus polymerase protein, Virology 152: 126–135.PubMedCrossRefGoogle Scholar
  81. Kendal, A. P., Goldfield, M., Noble, G. R., and Dowdle, W. R., 1977, Identification and preliminary antigenic analysis of swine influenza-like virus isolated during an influenza outbreak at Fort Dix, New Jersey, J. Infect. Dis. 136: 381–385.CrossRefGoogle Scholar
  82. Kendal, A. P., Noble, G. R., Skehel, J. J., and Dowdle, W. R., 1978, Antigenic similarity of influenza A (H1N1) viruses from epidemics in 1977–1978 to “Scandinavian” strains isolated in epidemics of 1950–1951, Virology 89: 632–636.PubMedCrossRefGoogle Scholar
  83. Kilbourne, E. D., and Murphy, J. S., 1960, Genetic studies of influenza viruses. I. Viral morphology and growth capacity as exchangeable genetic traits. Rapid in vivo adaptation of early passage Asian strain isolates by combination with PR8, J. Exp. Med. 111: 387–415.PubMedCrossRefGoogle Scholar
  84. Kilbourne, E. D., Schulman, J. L., Schild, G. C., Schloer, G., Swanson, J., and Bucher, D., 1971, Correlated studies of a recombinant influenza virus vaccine. I. Derivation and characterization of virus and vaccine, J. Infect. Dis. 124: 449–462.PubMedCrossRefGoogle Scholar
  85. Krystal, M., Elliott, R. M., Benz, E. W., Young, J. F., and Palese, P., 1982, Evolution of influenza A and B viruses: Conservation of structural features in the hemagglutinin gene, Proc. Natl. Acad. Sci. USA 79: 4800–4804.PubMedCrossRefGoogle Scholar
  86. Krystal, M., Young, J. F., Palese, P., Wilson, I. A., Skehel, J. J., and Wiley, D. C., 1983, Sequential mutations in the hemagglutinins of influenza B virus isolates: Definition of antigenic domains, Proc. Natl. Acad. Sci. USA 80: 4527–4531.PubMedCrossRefGoogle Scholar
  87. Lamb, R. A., 1983, The influenza virus RNA segments and their encoded proteins, in: Genetics of Influenza Viruses ( P. Palese and D. W. Kingsbury, eds.), pp. 21–69, Springer-Verlag, New York.Google Scholar
  88. Lamb, R. A., and Choppin, P. W., 1981, Identification of a second protein (M2) encoded by RNA segment 7 of influenza virus, Virology 112: 729–737.PubMedCrossRefGoogle Scholar
  89. Lamb, R. A., and Lai, C.-J., 1981, Conservation of the influenza virus membrane protein (M1) amino acid sequence and an open reading frame of RNA segment 7 encoding a second protein (M2) in H1N1 and H3N2 strains, Virology 112: 746–751.PubMedCrossRefGoogle Scholar
  90. Laver, W. G., and Webster, R. G., 1973, Studies on the origin of pandemic influenza. III. Evidence implicating duck and equine influenza viruses as possible progenitors of the Hong Kong strain of human influenza, Virology 51: 383–391.PubMedCrossRefGoogle Scholar
  91. Laver, W. G., Air, G. M., Webster, R. G., and Markoff, L. J., 1982, Amino acid sequence changes in antigenic variants of type A influenza virus N2 neuraminidase, Virology 122: 450–460.PubMedCrossRefGoogle Scholar
  92. Leider, J. M., Palese, P., and Smith, F. I., 1988, Determination of the mutation rate of a retrovirus, J. Virol. 62: 3084–3091.PubMedGoogle Scholar
  93. Li, W.-H., and Gojobori, T., 1983, Rapid evolution of goat and sheep globin genes following gene duplication, Mol. Biol. Evol. 1: 94–108.PubMedGoogle Scholar
  94. Londo, D. R., Davis, A. R., and Nayak, D. P., 1983, Complete nucleotide sequence of the nucleoprotein gene of influenza B virus, J. Virol. 47: 642–648.PubMedGoogle Scholar
  95. Lu, B. L., Webster, R. G., Brown, L. E., and Nerome, K., 1983, Heterogenicity of influenza B viruses, Bull. WHO 61: 681–687.Google Scholar
  96. Lubeck, M. D., Schulman, J. L., and Palese, P., 1978, Susceptibility of influenza A viruses to amantadine is determined by the gene coding for M protein, J. Virol. 28: 710–716.PubMedGoogle Scholar
  97. Lubeck, M. D., Schulman, J. L., and Palese, P., 1980, Antigenic variants of influenza viruses: Marked differences in the frequencies of variants selected with different monoclonal antibodies, Virology 102: 458–462.PubMedCrossRefGoogle Scholar
  98. Lutley, R., Petursson, C., Palsson, P. A., Georgsson, G., Klein, J., and Nathansson, N., 1983, Antigenic drift in visna: Virus variation during longterm infection of Icelandic sheep, J. Gen. Virol. 64: 1433–1440.PubMedCrossRefGoogle Scholar
  99. Maassab, H. F., 1968, Adaptation and growth characteristics of influenza virus at 25°C, Nature (Lond.) 219: 645–646.CrossRefGoogle Scholar
  100. Markoff, L., and Lai, C.-J., 1982, Sequence of the influenza A/Udom/72 (H3N2) virus neur- aminidase gene as determined from cloned full-length DNA, Virology 119: 288–297.PubMedCrossRefGoogle Scholar
  101. Markushin, S., Ghiasi, H., Sokolov, N., Shilov, A., Sinitsin, B., Brown, D., Klimov, A., and Nayak, D., 1988, Nucleotide sequence of RNA segment 7 and the predicted amino sequence of Ml and M2 proteins of FPV/Weybridge (H7N7) and WSN (H1N1) influenza viruses, Virus Res. 10: 263–272.PubMedCrossRefGoogle Scholar
  102. Martinez, C., Del Rio, L., Portela, A., Domingo, E., and Ortin, J., 1983, Evolution of the influenza virus neuraminidase gene during drift of the N2 subtype, Virology 130: 539–545.PubMedCrossRefGoogle Scholar
  103. Medvedeva, T. E., Gordon, M. A., Ghendon, Y. Z., Klimov, A. I., and Alexandrova, G. I., 1983, Attenuated influenza B virus recombinants obtained by crossing of B/England/2608/76 virus with a cold-adapted B/Leningrad/14/17/55 strain, Acta Virol. 27: 311.Google Scholar
  104. Meier-Ewert, H., Petri, T., and Bishop, D. H. L., 1981, Oligonucleotide fingerprint analyses of influenza C virion RNA recovered from five different isolates, Arch. Virol. 67: 141–147.PubMedCrossRefGoogle Scholar
  105. Minor, P. D., Schild, G. C., Bootman, J., Evans, D. M. A., Ferguson, M., Reeve, P., Spitz, M., Stanway, G., Cann, A. J., Hauptmann, R., Clarke, L. D., Mountford, R. C., and Almond, J. W., 1983, Location and primary structure of a major antigenic site for poliovirus neutralization, Nature (Lund.) 310: 674–679.CrossRefGoogle Scholar
  106. Miyamura, K., Tanimura, M., Takeda, N., Kono, R., and Yamazaki, S, 1986, Evolution of enterovirus 70 in nature: All isolates were recently derived from a common ancestor, Arch. Virol. 89: 1–14.PubMedCrossRefGoogle Scholar
  107. Murphy, B. R., and Chanock, R. M., 1981, Genetic approaches to the prevention of influenza A virus infection, in: Genetic Variation among Influenza Viruses ( D. Nayak, ed.), pp. 601–615, Academic, Orlando, Florida.Google Scholar
  108. Murphy, B. R., Sly, D. L., Tierney, E. L., Hosier, E. L., Massicot, J. G., and Hinshaw, V. S., 1982, Influenza A reassortant virus derived from avian and human influenza A virus is attenuated and immunogenic in monkeys, Science 218: 1330–1332.PubMedCrossRefGoogle Scholar
  109. Naeve, C. W., Hinshaw, V. S., and Webster, R. G., 1984, Mutations in the hemagglutinin receptor-binding site can change the biological properties of an influenza virus, J. Virol. 51: 567–569.PubMedGoogle Scholar
  110. Nakada, S., Creager, R. S., Krystal, M., Aaronson, R. P., and Palese, P., 1984a, Influenza C virus hemagglutinin: Comparison with influenza A and B virus hemagglutinins, J. Virol. 50: 118–124.PubMedGoogle Scholar
  111. Nakada, S., Creager, R. S., Krystal, M., and Palese, P., 1984b, Complete nucleotide sequence of the influenza C/California/78 virus nucleoprotein gene, Virus Res. 1: 433–441.PubMedCrossRefGoogle Scholar
  112. Nakada, S., Graves, P. N., and Palese, P., 1986, The influenza C virus NS gene: Evidence for a spliced mRNA and a second NS gene product (NS2 protein), Virus Res. 4: 263–273.PubMedCrossRefGoogle Scholar
  113. Nakajima, S., Takeuchi, Y., and Nakajima, K., 1988, Location on the evolutionary tree of influenza H3 hemagglutinin genes of Japanese strains isolated during the 1985–86 season, Epidemiol. Infect. 100: 301–310.PubMedCrossRefGoogle Scholar
  114. Nakajima, K., Desselberger, U., and Palese, P., 1978, Recent human influenza A (H1N1) viruses are closely related genetically to strains isolated in 1950, Nature (Lond.) 274: 334–339.CrossRefGoogle Scholar
  115. Narayan, O., Griffin, D. E., and Chase, J., 1977, Antigenic shift of visna virus in persistently infected sheep, Science 197: 376–378.PubMedCrossRefGoogle Scholar
  116. Newton, S. E., Air, G. M., Webster, R. G., and Laver, W. G., 1983, Sequence of the hemagglutinin gene of influenza virus A/Memphis/1/71 and previously uncharacterized monoclonal antibody-derived variants, Virology 128: 495–501.PubMedCrossRefGoogle Scholar
  117. Norton, G. P., Tanaka, T., Tobita, K., Nakada, S, Buonagurio, D. A., Greenspan, D., Krystal, M., and Palese, P., 1987, Infectious influenza A and B virus variants with long carboxyl terminal deletions in the NS1 polypeptide, Virology 156: 204–213.PubMedCrossRefGoogle Scholar
  118. O’Callaghan, R. J., Gohd, R. S., and Labat, D. D., 1980, Human antibody to influenza C virus: Its age-related distribution and distinction from receptor analogs, Infect. Immun. 30: 500–505.PubMedGoogle Scholar
  119. Ortin, J., Martinez, C., Del Rio, L., Davila, M., Lopez-Galindez, C., Villanueva, N., and Domingo, E., 1983, Evolution of the nucleotide sequence of influenza virus RNA segment 7 during drift of the H3N2 subtype, Gene 23: 233–239.PubMedCrossRefGoogle Scholar
  120. Oxford, J. S., Corcoran, T., and Schild, G. C., 1981, Intratypic electrophoretic variation of structural and non-structural polypeptides of human influenza A viruses, J. Gen. Virol. 56: 431–436.PubMedCrossRefGoogle Scholar
  121. Oxford, J. S., Klimov, A. I., Corcoran, T., Ghendon, Y. Z., and Schild, G. C., 1984, Biochemical and serological studies of influenza B viruses: Comparisons of historical and recent isolates, Virus Res. 1: 241–258.PubMedCrossRefGoogle Scholar
  122. Palese, P., 1977, The genes of influenza virus, Cell 10: 1–10.PubMedCrossRefGoogle Scholar
  123. Palese, P., and Young, J. F., 1982, Variation of influenza A, B, and C viruses, Science 215: 1468–1474.PubMedCrossRefGoogle Scholar
  124. Parvin, J. D., Young, J. F., and Palese, P., 1983, Nonsense mutations affecting the lengths ofGoogle Scholar
  125. the NSI nonstructural proteins of influenza A virus isolates, Virology 128:512–517Google Scholar
  126. Parvin, J. D., Moscona, A., Pan, W. T., Leider, J. M., and Palese, P., 1986, Measurement of the mutation rates of animal viruses: Influenza A virus and poliovirus type 1, J. Virol. 59: 377–383.PubMedGoogle Scholar
  127. Petursson, G., Nathanson, N., Georgsson, G., Panitch, H., and Palsson, P. A., 1976, Pathogenesis of visna, sequential virologie, serologic and pathologic studies, Lab. Invest. 35: 402–412.PubMedGoogle Scholar
  128. Portner, A., Webster, R. G., and Bean, W. J., 1980, Similar frequencies of antigenic variants in Sendai, vesicular stomatitis, and influenza A viruses, Virology 104: 235–238.PubMedCrossRefGoogle Scholar
  129. Prabhakar, B. S., Haspel, M. V., McClintock, P. R., and Notkins, A. L., 1982, High frequency of antigenic variants among naturally occurring human Coxsackie B4 virus isolates identified by monoclonal antibodies, Nature (Lund.) 300: 374–376.CrossRefGoogle Scholar
  130. Raymond, R. L., Caton, A. J., Cox, N. J., Kendal, A. P., and Brownlee, G. G., 1986, The antigenicity and evolution of influenza Hl haemagglutinin, from 1950–1957 and 19771983: Two pathways from one gene, Virology 148: 275–287.PubMedCrossRefGoogle Scholar
  131. Ricco-Hesse, R., Pallansch, M. A., Nottay, B. K., and Kew, O., 1986, Natural distribution of wild type 1 poliovirus genotypes, in: Positive Strand RNA Viruses, UCLA Symposium on Molecular and Cellular Biology, New Series, Vol. 54 ( M. A. Brinton and R. Rueckert, eds.), pp. 477–486, Liss, New York.Google Scholar
  132. Robertson, J. S., Naeve, C. W., Webster, R. G., Bootman, J. S., Newman, R., and Schild, G., 1985, Alterations in the hemagglutinin associated with adaptation of influenza B virus to growth in eggs, Virology 143: 166–174.PubMedCrossRefGoogle Scholar
  133. Rogers, G. N., Paulson, J. C., Daniels, R. S., Skehel, J. J., Wilson, I. A., and Wiley, D. C., 1983, Single amino acid substitutions in influenza hemagglutinin change receptor binding specificity, Nature (Land.) 304: 76–78.CrossRefGoogle Scholar
  134. Rott, R., Orlich, M., and Scholtissek, C., 1979, Correlation of pathogenicity and gene constellation of influenza A viruses. III. Nonpathogenic recombinants derived from highly pathogenic parent strains, J. Gen. Virol. 44: 471–477.PubMedCrossRefGoogle Scholar
  135. Rott, R., Orlich, M., Klenk, H.-D., Wang, M. L., Skehel, J. J., and Wiley, D. C., 1984, Studies on the adaptation of influenza viruses to MDCK cells, EMBO J. 3: 3329–3332.PubMedGoogle Scholar
  136. Salinovitch, O., Payne, S. L., Montelaro, R. C., Hussain, K. A., Issel, C. J., and Schnorr, K. L., 1986, Rapid emergence of novel antigenic and genetic variants of equine infectious anemia virus during persistent infection, 1. Virol. 57: 71–80.Google Scholar
  137. Samokhvalov, E. I., Karginov, V. A., Yuferov, V. P., Tschishkov, V. A., Blinov, V. M., Vasilenko, L. W., Uryvaev, L. W., and Zhdanov, V. M., 1985, Primary structure of RNA segment 7 of A/USSR/90/77 (H1N1) influenza virus, Bioorg. Khim. 11: 1080–1085.PubMedGoogle Scholar
  138. Schild, G. C., Oxford, J. S., and Newman, R. W., 1979, Evidence for antigenic variation in influenza A nucleoprotein, Virology 93: 569–573.PubMedCrossRefGoogle Scholar
  139. Scholtissek, C., 1986, Molecular biological background of the species and organ specificity of influenza A viruses, Angew. Chem. Int. Ed. Engl. 25: 47–56.CrossRefGoogle Scholar
  140. Scholtissek, C., Burger, H., Kistner, O., and Shortridge, K. F., 1985, The nucleoprotein as a possible major factor in determining host specificity of influenza H3N2 viruses, Virology 147: 287–294.PubMedCrossRefGoogle Scholar
  141. Scholtissek, C., Rott, R., Orlich, M., Harms, E., and Rohde, W., 1977, Correlation of pathogenicity and gene contellation of an influenza A virus (fowl plague). I. Exchange of a single gene, Virology 81: 74–80.PubMedCrossRefGoogle Scholar
  142. Scholtissek, C., Rohde, W., Von Hoyningen, V., and Rott, R., 1978a, On the origin of the human influenza virus subtypes H2N2 and H3N2, Virology 87: 13–20.PubMedCrossRefGoogle Scholar
  143. Scholtissek, C., Von Hoyningen, V., and Rott, R., 1978b, Genetic relatedness between the new 1977 epidemic strains (H1N1) of influenza and human influenza strains isolated between 1947 and 1957 (H1N1), Virology 89: 613–617.PubMedCrossRefGoogle Scholar
  144. Scholtissek, C., Vallbracht, A., Flehmig, B., and Rott, R., 1979, Correlation of pathogenicity and gene constellation of influenza A viruses. II. Highly neurovirulent recombinants derived from non-neurovirulent or weakly neurovirulent parent virus strains, Virology 95: 492–500.PubMedCrossRefGoogle Scholar
  145. Schreier, E., Roeske, H., Driesel, G., Kunkel, U., Petzold, D. R., Berlinghoff, R., and Michel, S., 1988, Complete nucleotide sequence of the neuraminidase gene of the human influenza virus A/Chile/1/83 (H1N1) Arch. Virol. 99: 271–276.PubMedCrossRefGoogle Scholar
  146. Schulman, J. L., 1983, Virus-determined differences in the pathogenesis of influenza viruses, in: Genetics of Influenza Viruses ( P. Palese and D. W. Kingsbury, eds.), pp. 305–320, Springer-Verlag, New York.Google Scholar
  147. Schulman, J. L., and Kilbourne, E. D., 1969, Independent variation in nature of hemagglutinin and neuraminidase antigens of influenza virus: Distinctiveness of hemagglutinin antigen of Hong Kong/68 virus, Proc. Natl. Acad. Sci. USA 63: 326–333.PubMedCrossRefGoogle Scholar
  148. Schulman, J. L., and Palese, P., 1977, Virulence factors of influenza viruses. WSN virus neuraminidase is required for productive infection of MDBK cells, J. Virol. 24: 170–176.PubMedGoogle Scholar
  149. Schulman, J. L., and Palese, P., 1978, Biological properties of influenza A/Hong Kong and PR8 viruses: Effects of genes for matrix protein and nucleoprotein on virus yield in embryonated eggs, in: Negative Strand Viruses and the Host Cell ( B. W. J. Mahy and R. D. Barry, eds.), pp. 663–674, Academic, Orlando, Florida.Google Scholar
  150. Sedivy, J. M., Capone, J. P., RajBhandary, U. L., and Sharp, P. A., 1987, An inducible mam- malian amber suppressor: Propagation of a poliovirus mutant, Cell 50: 379–389.PubMedCrossRefGoogle Scholar
  151. Sivasubramanian, N., and Nayak, D. P., 1982, Sequence analysis of the polymerase 1 gene and the secondary structure prediction of polymerase 1 protein of human influenza virus A/WSN/33, J. Virol. 44: 321–329.PubMedGoogle Scholar
  152. Skehel, J. J., and Wiley, D. C., 1988, Antigenic variation in influenza virus hemagglutinins, in: RNA Genetics, Vol. III: Variability of RNA Genomes ( E. Domingo, J. J. Holland, and P. Ahlquist, eds.), pp. 139–146, CRC Press, Boca Raton, Florida.Google Scholar
  153. Sleigh, M. J., Both, G. W., Underwood, P. A., and Bender, V. J., 1981, Antigenic drift in the hemagglutinin of the Hong Kong influenza subtype: Correlation of amino acid changes with alterations in viral antigenicity, J. Virol. 37: 845–853.PubMedGoogle Scholar
  154. Snyder, M. H., Buckler-White, A. J., London, W. T., Tierney, E. L., and Murphy, B. R., 1987, The avian influenza virus nucleoprotein gene and a specific constellation of avian and human virus polymerase genes each specify attenuation of avian—human influenza A/pintail/79 reassortant viruses for monkeys, J. Virol. 61: 2857–2863.PubMedGoogle Scholar
  155. Sobrino, F., Palma, E. L., Beck, E., Davila, M., de la Torre, J. C., Negro, P., Villanueva, N., Ortin, J., and Domingo, E., 1986, Fixation of mutations in the viral genome during an outbreak of foot-and-mouth disease: Heterogeneity and rate variations, Gene 50: 149–159.PubMedCrossRefGoogle Scholar
  156. Starcich, B. R., Hahn, B. H., Shaw, G. M., McNeely, P. D., Modrow, S., Wolf, H., Parks, E. S., Parks, W. P., Josephs, S. F., Gallo, R. C., and Wong-Staal, F., 1986, Identification and characterization of conserved and variable regions in the envelope gene of HTLVIII/ LAV, the retrovirus of AIDS, Cell 45: 637–648.PubMedCrossRefGoogle Scholar
  157. Steinhauer, D. A., and Holland, J. J., 1986, Direct method for quantitation of extreme polymerase error frequencies at selected single base sites in viral RNA, J. Virol. 57: 219–228.PubMedGoogle Scholar
  158. Stoeckle, M. Y., Shaw, M. W., and Choppin, P. W., 1987, Segment-specific and common nucleotide sequences in the non-coding regions of influenza B virus genome RNAs, Proc. Natl. Acad. Sci. USA 84: 2703–2707.PubMedCrossRefGoogle Scholar
  159. Sugiura, A., and Ueda, M., 1980, Neurovirulence of influenza virus in mice. I. Neurovirulence of recombinants between virulent and avirulent strains, Virology 101: 440–449.PubMedCrossRefGoogle Scholar
  160. Takeda, N., Miyamura, K., Ogino, T., Natori, K., Yamazaki, S, Sakurai, N., Nakazono, N., Ishii, K., and Kono, R., 1984, Evolution of enterovirus type 70: Oligonucleotide mapping analysis of RNA genome, Virology 134: 375–388.PubMedCrossRefGoogle Scholar
  161. Tanimura, M., Miyamura, K., and Takeda, N., 1985, Construction of a phylogenetic tree of enterovirus 70, Jpn. J. Genet. 60: 137–150.CrossRefGoogle Scholar
  162. Thormar, H., Barshatzky, M. R., Arnesen, K., and Kozlowski, P. B., 1983, The emergence of antigenic variants is a rare event in long-term visna virus infection in vivo, J. Gen. Virol. 64: 1427–1432.PubMedCrossRefGoogle Scholar
  163. Tian, S. F., Buckler-White, A. J., London, W. T., Reck, L. J., Chanock, R. M., and Murphy, B. R., 1985, Nucleoprotein and membrane protein genes are associated with restriction of replication of influenza A/Mallard/NY/78 virus and its reassortants in squirrel monkey respiratory tract, J. Virol. 53: 771–775.PubMedGoogle Scholar
  164. Van Wyke, K. L., Yewdell, J. W., Reck, L. J., and Murphy, B. R., 1984, Antigenic characterization of influenza A virus matrix protein with monoclonal antibodies, J. Virol. 49: 248–252.PubMedGoogle Scholar
  165. Van Wyke, K. L., Hinshaw, V. S., Bean, W. J., and Webster, R. G., 1980, Antigenic variation of influenza A virus nucleoprotein detected with monoclonal antibodies, J. Virol. 35: 24–30.PubMedGoogle Scholar
  166. Verhoeyen, M., Fang, R., Min Jou, W., Devos, R., Huylebroeck, D., Saman, E., and Fiers, W., 1980, Antigenic drift between the haemagglutinin of the Hong Kong influenza strains A/Aichi/2/68 and A/Victoria/3/75, Nature (Lond.) 286: 771–776.CrossRefGoogle Scholar
  167. Verhoeyen, M., Van Rompuy, L., Min Jou, W., Huylebroeck, D., and Fiers, W., 1983, Complete nucleotide sequence of the influenza B/Singapore/222/79 virus hemagglutinin gene and comparison with the B/Lee/40 hemagglutinin, Nucl. Acids Res. 11: 4703–4712.PubMedCrossRefGoogle Scholar
  168. Vlasak, R., Krystal, M., Nacht, M., and Palese, P., 1987, The influenza C virus glycoprotein (HE) exhibits receptor-binding (hemagglutinin) and receptor-destroying (esterase) activities, Virology 160: 419–425.PubMedCrossRefGoogle Scholar
  169. Ward, C. W., and Dopheide, T. A., 198la, Amino acid sequence and oligosaccharide distribution of the hemagglutinin from an early Hong Kong influenza virus variant A/Aichi/2/68 (X-31), Biochem. J. 193: 953–962.Google Scholar
  170. Ward, C. W., and Dopheide, T. A., 198 lb, Evolution of the Hong Kong influenza A subtype, Biochem. J. 195: 337–340.Google Scholar
  171. Webster, R. G., and Berton, M. T., 1981, Analysis of antigenic drift in the hemagglutinin molecule of influenza B virus with monoclonal antibodies, J. Gen. Virol. 54: 243–251.PubMedCrossRefGoogle Scholar
  172. Webster, R. G., Campbell, C. H., and Granoff, A., 1971, The in vivo production of “new” influenza viruses. I. Genetic recombination between avian and mammalian influenza viruses, Virology 44: 317–328.PubMedCrossRefGoogle Scholar
  173. Webster, R. G., Hinshaw, V. S., and Laver, W. G., 1982, Selection and analysis of antigenic variants of the neuraminidase of N2 influenza viruses with monoclonal antibodies, Virology 117: 93–104.PubMedCrossRefGoogle Scholar
  174. Webster, R. G., Kawaoka, Y., and Bean, W. J., 1986, Molecular changes in A/chicken/Pennsylvania/83 (H5N2) influenza virus associated with acquisition of virulence, Virology 149: 165–173.PubMedCrossRefGoogle Scholar
  175. Webster, R. G., and Rott, R., 1987, Influenza virus A pathogenicity: The pivotal role of hemagglutinin, Cell 50: 665–666.PubMedCrossRefGoogle Scholar
  176. White, J., Kielan, M., and Helenius, A., 1983, Membrane fusion proteins of enveloped animal viruses, Q. Rev. Biophys. 16: 151–195.PubMedCrossRefGoogle Scholar
  177. Winter, G., and Fields, S., 1980, Cloning of influenza cDNA into M13: The sequence of the RNA segment encoding the A/PR/8/34 matrix protein, Nucl. Acids Res. 8: 1965–1974.PubMedCrossRefGoogle Scholar
  178. Winter, G., and Fields, S., 1981, The structure of the gene encoding the nucleoprotein of human influenza virus A/PR/8/34, Virology 114: 423–428.PubMedCrossRefGoogle Scholar
  179. Winter, G., and Fields, S., 1982, Nucleotide sequence of human influenza A/PR/8/34 segment 2, Nucl. Acids Res. 10: 2135–2143.PubMedCrossRefGoogle Scholar
  180. Winter, G., Fields, S., and Brownlee, G. G., 1981, Nucleotide sequence of the haemagglutinin of a human influenza virus Hl subtype, Nature (Lond.) 292: 72–75.CrossRefGoogle Scholar
  181. Yamashita, M., Krystal, M., and Palese, P., 1988a, Evidence that the matrix protein of influenza C virus is coded for by a spliced mRNA, J. Virol. 62: 3348–3355.PubMedGoogle Scholar
  182. Yamashita, M., Krystal, M., Fitch, W. M., and Palese, P., 1988b, Influenza B virus evolution: Co-circulating lineages and comparison of evolutionary patterns with those of influenza A and C viruses, Virology 163: 112–123.PubMedCrossRefGoogle Scholar
  183. Yewdell, J. W., Caton, A. J., and Gerhard, W., 1986, Selection of influenza A virus adsorptive mutants by growth in the presence of a mixture of monoclonal anti-hemagglutinin antibodies, J. Virol. 57: 623–628.PubMedGoogle Scholar
  184. Young, J. F., and Palese, P., 1979, Evolution of human influenza A viruses in nature: Recombination contributes to genetic variation of H1N1 strains, Proc. Natl. Acad. Sci. USA 76: 6547–6551.PubMedCrossRefGoogle Scholar
  185. Young, J. F., Desselberger, U., and Palese, P., 1979, Evolution of human influenza A viruses in nature: Sequential mutations in the genomes of new H1N1 isolates, Cell 18: 73–83.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Frances I. Smith
    • 1
  • Peter Palese
    • 1
  1. 1.Department of MicrobiologyMount Sinai School of MedicineNew YorkUSA

Personalised recommendations