1887

Abstract

Five monoclonal antibody (MAb) neutralization escape mutants of respiratory syncytial virus (RSV) were produced by growing the Long strain RSV (group A virus) in the presence of a neutralizing, group cross-reactive MAb specific for the attachment protein (G). Four viruses (RSV-2, −6, −14 and −15) had amino acid replacements clustered within a highly conserved centrally located 13 amino acid region (position 164–176). Reactivity with group A- specific MAbs and with polyclonal anti-G serum was maintained and growth kinetics were unaffected. An additional virus (RSV-3) had four amino acid substitutions in the cytoplasmic tail and transmembrane region of G, and had restricted growth and formed small syncytia. Immunofluorescent and Western blot analysis indicated that G protein was not membrane associated and had reduced incorporation into the virion, thereby escaping neutralization by L9 and polyclonal anti-G serum. The predominant form of G produced by RSV-3 was found in infected cell supernatants, consistent with the size of secreted G.

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1998-03-01
2024-03-28
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References

  1. Akerlind-Stopner B., Utter G., Mufson M., Orvell C., Lerner R., Norrby E. 1990; A subgroup-specific antigenic site in the G protein of respiratory syncytial virus forms a disulfide-bonded loop. Journal of Virology 64:5143–5148
    [Google Scholar]
  2. Anderson L. J., Hierholzer J. C., Tsou C., Hendry R. M., Fernie B. F., Stone Y., McIntosh K. 1985; Antig enic characterization of respiratory syncytial virus strains with monoclonal antibodies. Journal of Infectious Diseases 151:626–633
    [Google Scholar]
  3. Anderson L. J., Hendry R. M., Pierik L. T., Tsou C., McIntosh K. 1991; Multicenter study of strains of respiratory syncytial virus. Journal of Infectious Diseases 163:687–692
    [Google Scholar]
  4. Ausubel F. M., Brent R., Kingston R. E., Moore D. D., Smith J. A., Seidman J. G., Struhl K. 1997 Current Protocols in Molecular Biology New York: John Wiley & Sons;
    [Google Scholar]
  5. Bass B. L., Weintraub H., Cattaneo R., Billeter M. A. 1989; Biased hypermutation of viral RNA genomes could be due to unwinding/ modification of double-stranded RNA. Cell 56:331
    [Google Scholar]
  6. Cane P. A., Pringle C. R. 1991; Respiratory syncytial virus heterogeneity during an epidemic : analysis by limited nucleotide sequencing (SH gene) and restriction mapping (N gene). Journal of General Virology 72:349–357
    [Google Scholar]
  7. Cane P. A., Pringle C. R. 1995; Evolution of subgroup A respiratory syncytial virus : evidence for progressive accumulation of amino acid changes in the attachment protein. Journal of Virology 69:2918–2925
    [Google Scholar]
  8. Cane P. A., Matthews D. A., Pringle C. R. 1991; Identification of variable domains of the attachment (G) protein of subgroup A respiratory syncytial viruses. Journal of General Virology 72:2091–2096
    [Google Scholar]
  9. Collins P. 1991; The molecular biology of human respiratory syncytial viruses (RSV) of the genus Pneumovirus . In The Paramyxoviruses pp 103–162 Kingsbury D. W. Edited by New York: Plenum;
    [Google Scholar]
  10. Collins P. L., Mottet G. 1992; Oligomerization and post translation processing of glycoprotein G of human respiratory syncytial virus : altered, O-glycosylation in the presence of brefeldin A. Journal of General Virology 73:849–863
    [Google Scholar]
  11. Doreleijers J. F., Langedijk J. P. M., Hard K., Boelens R., Rullmann J. A. C., Schaaper W. M. M., van Oirschot J. T., Kaptein R. 1996; Solution structure of the immunodominant region of protein G of bovine respiratory syncytial virus. Biochemistry 35:14684–14688
    [Google Scholar]
  12. Fernie B. F., Dapolito G., Cote P. J., Gerin J. 1985; Kinetics of synthesis of respiratory syncytial virus glycoproteins. Journal of General Virology 66:1983–1990
    [Google Scholar]
  13. Garcia O., Martin M., Dopazo J., Arbiza J., Frabasile S., Russi J., Hortal M., Perez-Brena P., Martinez I., Garcia-Barreno B., Melero J. A. 1994; Evolutionary pattern of human respiratory syncytial virus (subgroup A) : cocirculating lineages and correlation of genetic and antigenic changes in the G glycoprotein. Journal of Virology 68:5448–5459
    [Google Scholar]
  14. Garcia-Barreno B., Delgado T., Akerlind B., Norrby E., Melero J. A. 1992; Location of the epitope recognized by monoclonal antibody 63G on the primary structure of human respiratory syncytial virus G glycoprotein and the ability of synthetic peptides containing this epitope to induce neutralizing antibodies. Journal of General Virology 73:2625–2630
    [Google Scholar]
  15. Hendricks D. A., Baradaran K., McIntosh K., Patterson J. L. 1987; App earance of a soluble form of the G protein of respiratory syncytial virus in fluids of infected cells. Journal of General Virology 68:1705–1714
    [Google Scholar]
  16. Hendricks D. A., McIntosh K., Patterson J. L. 1988; Further characterization of the soluble form of the G glycoprotein of respiratory syncytial virus. Journal of Virology 62:2228–2233
    [Google Scholar]
  17. Huang Y. T., Collins P. L., Wertz G. W. 1985; Characterization of the 10 proteins of human respiratory syncytial virus : identification of a fourth envelope-associated protein. Virus Research 2:157–173
    [Google Scholar]
  18. Johnson P. R., Spriggs M. K., Olmsted R. A., Collins P. L. 1987; The G glycoprotein of human respiratory syncytial viruses of subgroups A and B : extensive sequence divergence between antigenically related proteins. Proceedings of the National Academy of Sciences, USA 84:5625–5629
    [Google Scholar]
  19. Kundu A., Avalos R. T., Sanderson C. M., Nayak D. P. 1996; Transmembrane domain of influenza virus neuraminidase, a type II protein, possesses an apical sorting signal in polarized MDCK cells. Journal of Virology 70:6508–6515
    [Google Scholar]
  20. Langedijk J. P. M., Schaaper W. M. M., Meloen R. H., van Oirschot J. T. 1996; Proposed three-dimensional model for the attachment protein G of respiratory syncytial virus. Journal of General Virology 77:1249–1257
    [Google Scholar]
  21. Levine S., Klaiber-Franco R., Paradiso P. 1987; Demonstration that glycoprotein G is the attachment protein of respiratory syncytial virus. Journal of General Virology 68:2521–2524
    [Google Scholar]
  22. Levine B., Jiang H. H., Kleeman L., Yang G. 1996; Effect of E2 envelope glycoprotein cytoplasmic domain mutations on Sindbis virus pathogenesis. Journal of Virology 70:1255–1260
    [Google Scholar]
  23. Li L., Coelingh K. L., Britt W. J. 1995; Human cytomegalovirus neutralizing antibody-resistant phenotype is associated with reduced expression of glycoprotein H. Journal of Virology 69:6047–6053
    [Google Scholar]
  24. Lichtenstein D. L., Roberts S. R., Wertz G. W., Ball L. A. 1996; Definition and functional analysis of the signal/anchor domain of the human respiratory syncytial virus glycoprotein G. Journal of General Virology 77:109–118
    [Google Scholar]
  25. Mitnaul L. J., Castrucci M. R., Murti K. G., Kawaoka Y. 1996; The cytoplasmic tail of influenza A virus neuraminidase (NA) affects NA incorporation into virions, virion morphology, and virulence in mice but is not essential for virus replication. Journal of Virology 70:873–879
    [Google Scholar]
  26. Mufson M. A., Orvell C., Rafnar B., Norrby E. 1985; Two distinct subtypes of human respiratory syncytial virus. Journal of General Virology 66:2111–2124
    [Google Scholar]
  27. Roberts S. R., Lichtenstein D., Ball L. A., Wertz G. W. 1994; The membrane-associated and secreted forms of the respiratory syncytial virus attachment glycoprotein G are synthesized from alternative initiation codons. Journal of Virology 68:4538–4546
    [Google Scholar]
  28. Rueda P., Garcia-Barreno B., Melero J. A. 1994; Loss of conserved cysteine residues in the attachment (G) glycoprotein of two human respiratory syncytial virus escape mutants that contain multiple A-G substitutions (hypermutations). Virology 198:653–662
    [Google Scholar]
  29. Simard C., Nadon F., Seguin C., Thien N. N., Binz H., Basso J., Laliberte J., Trudel M. 1997; Subgroup specific protection of mice from respiratory syncytial virus infection with peptides encompassing the amino acid region 174-187 from the G glycoprotein: the role of cysteinyl residues in protection. Vaccine 15:423–432
    [Google Scholar]
  30. Storch G. A., Park C. S. 1987; Monoclonal antibodies demonstrate heterogeneity in the G glycoprotein of prototype strains and clinical isolates of respiratory syncytial virus. Journal of Medical Virology 22:345–356
    [Google Scholar]
  31. Sullender W. M. 1995; Antigenic analysis of chimeric and truncated G proteins of respiratory syncytial virus. Virology 209:70–79
    [Google Scholar]
  32. Sullender W. M., Mufson M. A., Anderson L. J., Wertz G. W. 1991; Genetic diversity of the attachment protein of subgroup B respiratory syncytial viruses. Journal of Virology 65:5425–5434
    [Google Scholar]
  33. Trudel M., Nadon F., Seguin C., Binz H. 1991; Protection of BALB/c mice from respiratory syncytial virus infection by immunization with a synthetic peptide derived from the G-glycoprotein. Virology 185:749–757
    [Google Scholar]
  34. Walsh E. E., Hruska J. 1983; Monoclonal antibodies to respiratory syncytial virus proteins: Identification of the fusion protein. Journal of Virology 47:171–177
    [Google Scholar]
  35. Walsh E. E., Cote P. J., Fernie B. F., Schlesinger J. J., Brandriss M. W. 1986; Analysis of the respiratory syncytial virus fusion protein using monoclonal and polyclonal antibodies. Journal of General Virology 67:505–513
    [Google Scholar]
  36. Walsh E. E., Brandriss M., Schlesinger J. J. 1987; Immunological differences between the envelope glycoproteins of two strains of human respiratory syncytial virus. Journal of General Virology 68:2169–2176
    [Google Scholar]
  37. Walsh E. E., Hall C. B., Schlesinger J. J., Brandriss M., Hildreth S., Paradiso P. 1989; Comparison of antigenic sites of subtype-specific respiratory syncytial virus attachment proteins. JournalofGeneral Virology 70:2953–2961
    [Google Scholar]
  38. Wertz G. W., Collins P. L., Huang Y., Gruber C., Levine S., Ball L. A. 1985; Nucleotide sequence of the G protein gene of human respiratory syncytial virus reveals an unusual type of viral membrane protein. Proceedings of the National Academy of Sciences, USA 82:4075–4079
    [Google Scholar]
  39. Wertz G. W., Krieger M., Ball L. A. 1989; Structure and cell surface maturation of the attachment glycoprotein of human respiratory syncytial virus in a cell line deficient in O glycosylation. Journal of Virology 63:4767–4776
    [Google Scholar]
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