Structural characterization of respiratory syncytial virus fusion inhibitor escape mutants: homology model of the F protein and a syncytium formation assay

Morton, Craig J., Cameron, Rachel, Lawrence, Lynne J., Lin, Bo, Lowe, Melinda, Luttick, Angela, Mason, Anthony, McKimm-Breschkin, Jenny, Parker, Michael W., Ryan, Jane, Smout, Michael, Sullivan, Jayne, Tucker, Simon P., and Young, Paul R. (2003) Structural characterization of respiratory syncytial virus fusion inhibitor escape mutants: homology model of the F protein and a syncytium formation assay. Virology, 311 (2). pp. 275-288.

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Abstract

Respiratory syncytial virus (RSV) is a ubiquitous human pathogen and the leading cause of lower respiratory tract infections in infants. Infection of cells and subsequent formation of syncytia occur through membrane fusion mediated by the RSV fusion protein (RSV-F). A novel in vitro assay of recombinant RSV-F function has been devised and used to characterize a number of escape mutants for three known inhibitors of RSV-F that have been isolated. Homology modeling of the RSV-F structure has been carried out on the basis of a chimera derived from the crystal structures of the RSV-F core and a fragment from the orthologous fusion protein from Newcastle disease virus (NDV). The structure correlates well with the appearance of RSV-F in electron micrographs, and the residues identified as contributing to specific binding sites for several monoclonal antibodies are arranged in appropriate solvent-accessible clusters. The positions of the characterized resistance mutants in the model structure identify two promising regions for the design of fusion inhibitors.

Item ID: 28469
Item Type: Article (Research - C1)
ISSN: 1089-862X
Keywords: respiratory syncitial virus, assay, fusion protein, homology model, antiviral, inhibitor
Date Deposited: 10 Sep 2013 03:59
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1108 Medical Microbiology > 110804 Medical Virology @ 60%
11 MEDICAL AND HEALTH SCIENCES > 1114 Paediatrics and Reproductive Medicine > 111403 Paediatrics @ 10%
06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060106 Cellular Interactions (incl Adhesion, Matrix, Cell Wall) @ 30%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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