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Comparison of human respiratory syncytial virus A2 and 8/60 fusion glycoprotein gene sequences and mapping of sub‐group specific antibody epitopes
Author(s) -
Connor A.L.,
Bevitt D.J.,
Toms G.L.
Publication year - 2001
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/1096-9071(20000201)63:2<168::aid-jmv1012>3.0.co;2-u
Subject(s) - immunogen , epitope , biology , gene , virology , virus , glycoprotein , microbiology and biotechnology , peptide sequence , amino acid , genetics , monoclonal antibody , antibody
The fusion glycoprotein, F, of human respiratory syncytial virus is a principal target of neutralising antibodies and an important protective immunogen. Among sub‐group A strains of the virus the F gene is highly conserved. A comparison of F gene sequences of two sub‐group B strains, 8/60 and 18537, indicates that the gene also is conserved within this sub‐group. However, both limited sequence variability and antigenic variation occurs between F genes from different virus sub‐groups. Such variability may be important in the failure of natural‐ and vaccine‐induced immunity and it is thus important to identify the variable epitopes. Three anti‐F MAbs exhibiting sub‐group specific neutralisation and binding to recombinant F glycoprotein were studied. Comparison of A2 and 8/60 F gene sequences revealed 64 predicted varient amino acids. In order to map the variant amino acids responsible for sub‐group specific binding, three sets of chimaeric genes, in which different domains of A2 and 8/60 F were exchanged, were created and expressed. Sub‐group specificity mapped to the N‐terminal region of F1 for two MAbs (RS2B8 and RS348) and to the C‐terminal region for the third. By using site‐directed mutagenesis, sub‐group specific binding of MAbs RS2B8 and RS348 was attributed to a predicted loop region between residues 200 and 216. This loop carried four residues variant between the sub‐groups. Change of at least two was necessary to abrogate MAb binding. J. Med. Virol. 63:168–177, 2001. © 2001 Wiley‐Liss, Inc.