title: Amino acid variation within the fusion protein of respiratory syncytial virus subtype A and B strains during annual epidemics in South Africa.
abstract: Recent evidence of positive selection within the cytotoxic T-cell (CTL) epitopes of the highly conserved nucleoprotein of influenza virus raised the question of whether the CTL epitopes of Respiratory syncytial virus (RSV) are also affected by immune driven change over annual epidemics. The fusion protein (F-protein) of RSV is highly conserved within the two subtypes (A and B) and the most important target for the protective response. The position of various neutralizing epitopes has been mapped and characterized between RSV subtypes. CTL epitopes have also recently been mapped for the F-protein of subtype A, however variation within these epitopes between and within the subtypes has not been determined. To address this question, the F-proteins of 18 strains representative of all subgroup A and B genotypes identified in South Africa over a period of 5 years were sequenced. F-protein sequences were highly conserved within and between South African genotypes, with most variability occurring at the nucleotide level. Most of the amino acid differences identified within neutralizing and CTL epitopes were conserved within the subtypes, and therefore does not indicate immune selection. However, out of three CTL epitopes previously identified in subtype A, two (restricted to HLA B*57 and HLA A *01) were conserved only within subtype A, while the third (restricted to Cw*12) contained both subtype- and genotype-specific changes. These results suggest that most of the identified CTL epitopes are subtype A-specific and may not be recognized in subtype B viruses, while the HLA Cw*12 restricted epitope may also not be recognized efficiently in GA5 strains.
authors.affiliation: National Institute for Communicable Diseases, Private bag X4, Modderfonteinroad, 2131, Sandringham, South Africa.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Agenbach
authors.forename: Caroline T
authors.initials: CT
authors.lastname: Tiemessen
authors.forename: Marietjie
authors.initials: M
authors.lastname: Venter
mesh_terms: D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000235:genetics; D001483:Base Sequence; D004279:DNA, Viral / Q000235:genetics; D004196:Disease Outbreaks; D000939:Epitopes / Q000235:genetics; D014644:Genetic Variation; D006680:HLA Antigens; D006801:Humans; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D012367:RNA, Viral / Q000235:genetics; D018357:Respiratory Syncytial Virus Infections / Q000453:epidemiology* / Q000276:immunology / Q000821:virology*; D018113:Respiratory Syncytial Virus, Human / Q000145:classification / Q000235:genetics* / Q000276:immunology; D017386:Sequence Homology, Amino Acid; D013019:South Africa / Q000453:epidemiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014760:Viral Fusion Proteins / Q000235:genetics* / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D004279:DNA, Viral; D000939:Epitopes; D006680:HLA Antigens; D012367:RNA, Viral; D014760:Viral Fusion Proteins
references.citation: J Immunol. 1994 Jan 1;152(1):163-75
references.pmid: 8254189
references.citation: Nucleic Acids Res. 1997 Dec 15;25(24):4876-82
references.pmid: 9396791