1887

Journal of General Virology header logo

Volume 78, Issue 10

Antigenic structure of the human respiratory syncytial virus G glycoprotein and relevance of hypermutation events for the generation of antigenic variants Free

Abstract

A set of monoclonal antibodies (MAbs) specific for the attachment (G) glycoprotein of a recently isolated strain of human respiratory syncytial virus (HRSV) is described. Antibody reactivity with a series of HRSV isolates belonging to antigenic groups A and B identified three epitope categories: (i) or epitopes that were present in a limited set of viruses from the same antigenic group, (ii) epitopes shared by viruses from the same antigenic group and (iii) epitopes present in all HRSV isolates. Sequence analysis of escape mutants was used to map relevant antigenic sites of the G glycoprotein. Strain-specific epitopes were located preferentially in the variable C-terminal third of the G polypeptide, in agreement with previous studies of the Long strain. However, a new strain-specific epitope was mapped into another variable region, N-terminal to the cluster of cysteines in the G protein ectodomain. In contrast, the group-specific and conserved epitopes were located in the central conserved region of the G protein primary structure. These results, together with previous analysis of the Long strain, provide a detailed antigenic map of the HRSV attachment protein. Some mutants selected with group-specific antibodies contain multiple A-G substitutions (hypermutations) and lack one or two of the four cysteines which are conserved in all HRSV isolates. The genetic mechanism implicated in the generation of the hypermutated viruses and its relevance for the natural history of HRSV are discussed.

  • Published Online:
© Society for General Microbiology Ltd 1997
Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-78-10-2419
1997-10-01
2024-04-18
Loading full text...

Full text loading...

/deliver/fulltext/jgv/78/10/9349460.html?itemId=/content/journal/jgv/10.1099/0022-1317-78-10-2419&mimeType=html&fmt=ahah

References

  1. Akerlind-Stopner B., Utter G., Mufson M., Örvell C., Lerner R. A., Norrby E. 1990; A subgroup-specific antigenic site in the G protein of respiratory syncytial virus forms a disulphide-bonded loop. Journal of Virology 64:5143–5148
     [Google Scholar]
  2. Alansari H., Potgieter L. N. D. 1993; Nucleotide sequence analysis of the ovine respiratory syncytial virus G glycoprotein gene. Virology 196:873–877
     [Google Scholar]
  3. 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]
  4. Anderson L. J., Bingham P., Hierholzer J. C. 1988; Neutralization of respiratory syncytial virus by individual and mixtures of F and G protein monoclonal antibodies. Journal of Virology 62:4232–4238
     [Google Scholar]
  5. Bass B. L., Weintraub H., Cattaneo R., Billeter M. 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. 1997; Analysis of linear epitopes recognized by the primary human antibody response to a variable region of the attachment (G) protein of respiratory syncytial virus. Journal of Medical Virology in press
    [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., Mathews D. A., Pringle C. R. 1991; Identification of variable domains of the attachment (G) protein of subgroup A respiratory syncytial virus. Journal of General Virology 72:2091–2096
     [Google Scholar]
  9. Cane P. A., Thomas H. W., Simpson A. F., Evans J. E., Hart C. A., Pringle C. R. 1996; Analysis of the human serological immune response to a variable region of the attachment (G) protein of respiratory syncytial virus during primary infection. Journal of Medical Virology 48:253–261
     [Google Scholar]
  10. Cattaneo R., Schmid A., Eschle D., Backzo K., ter Meulen V., Billeter M. A. 1988; Biased hypermutation and other genetic changes in defective measles viruses in human brain infections. Cell 55:255–265
     [Google Scholar]
  11. Chanock R. M., Roizman B., Myers R. 1957; Recovery from infants with respiratory illness of a virus related to chimpanzee coryza agent (CCA). I. Isolation, properties and characterization. American Journal of Hygiene 66:281–290
     [Google Scholar]
  12. Collins P. L., Mottet G. 1992; Oligomerization and post-translational 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]
  13. Collins P. L., McIntosh K., Chanock R. M. 1996; Respiratory syncytial virus. In Fields Virology pp 1313–1351 Fields B. N., Knipe D. M., Howley P. M. Edited by Philadelphia: Lippincott-Raven;
     [Google Scholar]
  14. Cristina J., López J. A., Albo C., García-Barreno B., García J., Melero J. A., Portela A. 1990; Analysis of genetic variability of human respiratory syncytial virus by the RNase A mismatch cleavage method: subtype divergence and heterogeneity. Virology 174:126–134
     [Google Scholar]
  15. Doreleijers J. F., Langedijk J. P. M., Hard K., Boelens R., Rullmann J. A. C., Schaaper W. 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]
  16. Felder M.-P., Laugier D., Yatsula B., Dezélée P., Calothy G., Marx M. 1994; Functional and biological properties of an avian variant long terminal repeat containing multiple A to G conversions in the U3 sequence. Journal of Virology 68:4759–4767
     [Google Scholar]
  17. García O., Martín M., Dopazo J., Arbiza J., Frabasile S., Russi J., Hortal M., Perez-Breña P., Martínez I., García-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]
  18. García-Barreno B., Jorcano J. L., Aukenbauer T., López-Galindez C., Melero J. A. 1988; Participation of cytoskeletal intermediate filaments in the infectious cycle of human respiratory syncytial virus (RSV). Virus Research 9:307–322
     [Google Scholar]
  19. García-Barreno B., Palomo C., Peñas C., Delgado T., Perez-Breña P., Melero J. A. 1989; Marked differences in the antigenic structure of human respiratory syncytial virus F and G glycoproteins. Journal of Virology 63:925–932
     [Google Scholar]
  20. García-Barreno B., Portela A., Delgado T., López J. A., Melero J. A. 1990; Frame shift mutations as a novel mechanism for the generation of neutralization resistant mutants of human respiratory syncytial virus. EMBO Journal 12:4181–4187
     [Google Scholar]
  21. García-Barreno B., Delgado T., Akerlind-Stopner 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]
  22. García-Beato R., Martínez I., Francí C., Real F. X., García-Barreno B., Melero J. A. 1996; Host cell effect upon glycosylation and antigenicity of human respiratory syncytial virus G glycoprotein. Virology 221:301–309
     [Google Scholar]
  23. 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: 845625–5629
     [Google Scholar]
  24. 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]
  25. Levine S., Klaiser-Franco R., Paradiso P. R. 1987; Demonstration that glycoprotein G Is the attachment protein of respiratory syncytial virus. Journal of General Virology 68:2521–2524
     [Google Scholar]
  26. Lerch R. A., Anderson K., Wertz G. W. 1990; Nucleotide sequence analysis and expression from recombinant vectors demonstrate that the attachment protein G of bovine respiratory syncytial virus is distinct from that of human respiratory syncytial virus. Journal of Virology 64:5559–5569
     [Google Scholar]
  27. Melcher T., Maas S., Higuchi M., Keller W., Seeburg P. H. 1995; Editing of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor GluR-B pre-mRNA in vitro reveals site-selective adenosine to inosine conversion. Journal of Biological Chemistry 270:8566–8570
     [Google Scholar]
  28. Mufson M. A., Örvell C., Rafnar B., Norrby E. 1985; Two distinct subtypes of human respiratory syncytial virus. Journal of General Virology 66:2111–2124
     [Google Scholar]
  29. Mufson M. A., Belshe R. B., Örvell C., Norrby E. 1987; Subgroup characteristics of respiratory syncytial virus strains recovered from children with two consecutive infections. Journal of Clinical Microbiology 25:1535–1539
     [Google Scholar]
  30. Murphy D. G., Dimock K., Kang Y. 1991; Numerous transitions in human parainfluenza virus 3 RNA recovered from persistently infected cells. Virology 181:760–763
     [Google Scholar]
  31. Netter H. J., Wu T.-T., Bockol M., Cywinski A., Ryu W.-S., Tennant B. C., Taylor J. M. 1995; Nucleotide sequence stability of the genome of hepatitis delta virus. Journal of Virology 69:1687–1692
     [Google Scholar]
  32. Norrby E., Mufson M. A., Alexander H., Houghten R. A., Lerner R. A. 1987; Site-directed serology with synthetic peptides representing the large glycoprotein G of respiratory syncytial virus. Proceedings of the National Academy of Sciences USA: 846572–6576
     [Google Scholar]
  33. O’Hara P. J., Nichol S. T., Horoddyki F. M., Holland J. J. 1984; Vesicular stomatitis virus defective interfering particles can contain extensive genomic sequence rearrangements and base substitutions. Cell 36:915–924
     [Google Scholar]
  34. Palomo C., García-Barreno B., Peñas C., Melero J. A. 1991; The G protein of human respiratory syncytial virus: significance of carbohydrate side-chains and the C-terminal end to its antigenicity. Journal of General Virology 72:669–675
     [Google Scholar]
  35. Rueda P., Delgado T., Portela A., Melero J. A., García-Barreno B. 1991; Premature stop codons in the G glycoprotein of human respiratory syncytial viruses resistant to neutralization by monoclonal antibodies. Journal of Virology 65:3374–3378
     [Google Scholar]
  36. Rueda P., García-Barreno B., Melero J. A. 1994; Loss ofconserved 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]
  37. Rueda P., Palomo C., García-Barreno B., Melero J. A. 1995; The three C-terminal residues of human respiratory syncytial virus G glycoprotein (Long strain) are essential for integrity of multiple epitopes distinguishable by antiidiotypic antibodies. Viral Immunology 8:37–46
     [Google Scholar]
  38. Sanchez-Fauquier A., Villanueva N., Melero J. A. 1987; Isolation of cross-reactive, subtype-specific monoclonal antibodies against influenza virus HA1 and HA2 hemagglutinin subunits. Archives of Virology 97:251–265
     [Google Scholar]
  39. Stoch 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]
  40. Sullender W. M., Mufson M. A., Anderson L. J., Wertz G. W. 1991; Genetic diversity of the attachment protein of subgroup B respiratory syncytial virus. Journal of Virology 65:3855–3861
     [Google Scholar]
  41. Walsh E. E., Brandriss M. W., Schlesinger J. J. 1985; Purification and characterization of the respiratory syncytial virus fusion protein. Journal of General Virology 66:409–415
     [Google Scholar]
  42. Walsh E. E., Hall C. B., Schlesinger J. J., Brandriss M. W., Hildreth S., Paradiso P. 1989; Comparison of antigenic sites of subtype-specific respiratory syncytial virus attachment protein. Journal of General Virology 70:2953–2961
     [Google Scholar]
  43. Waris M. 1991; Pattern of respiratory syncytial virus epidemics in Finland: two-year cycles with alternative prevalence of groups A and B. Journal of Infectious Diseases 163:464–469
     [Google Scholar]
  44. Wertz G. W., Krieger M., Ball L. A. 1989; Structure and cell surface maturation of the attachment glycoprotein of human respiratory syncytial virus. Journal of Virology 63:4767–4776
     [Google Scholar]
  45. Yang J. H., Sklar P., Axel R., Maniatis T. 1995; Editing of glutamate receptor subunit B pre-mRNA in vitro by site-specific deamination of adenosine. Nature 374:77–81
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-78-10-2419
Loading
Antigenic structure of the human respiratory syncytial virus G glycoprotein and relevance of hypermutation events for the generation of antigenic variants
J. Gen. Virol. 78, 2419 (1997); https://doi.org/10.1099/0022-1317-78-10-2419
/content/journal/jgv/10.1099/0022-1317-78-10-2419
/content/journal/jgv/10.1099/0022-1317-78-10-2419
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error