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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

Lookup NU author(s): Professor Debra Bevitt, Emeritus Professor Geoffrey Toms

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Abstract

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. © 2001 Wiley-Liss, Inc.

Publication metadata

Author(s): Connor AL, Bevitt DJ, Toms GL

Publication type: Article

Publication status: Published

Journal: Journal of Medical Virology

Year: 2001

Volume: 63

Issue: 2

Pages: 168-177

ISSN (print): 0146-6615

ISSN (electronic): 1096-9071

Publisher: John Wiley & Sons, Inc.

URL: http://dx.doi.org/10.1002/1096-9071(20000201)63:2<168::AID-JMV1012>3.0.CO;2-U

DOI: 10.1002/1096-9071(20000201)63:2<168::AID-JMV1012>3.0.CO;2-U

PubMed id: 11170054

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