Structural characterization of respiratory syncytial virus fusion inhibitor escape mutants: homology model of the F protein and a syncytium formation assay
| Autor: | Angela Luttick, Lynne J. Lawrence, Melinda Lowe, Bo Lin, Michael W. Parker, Jayne Sullivan, Rachel Cameron, Michael J. Smout, J.L. McKimm-Breschkin, Jane Ryan, Craig J. Morton, Simon P. Tucker, Paul R. Young, Anthony J. Mason |
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| Rok vydání: | 2003 |
| Předmět: |
Models
Molecular Inhibitor Protein Conformation viruses Molecular Sequence Data Assay Respiratory syncytial virus Biology Antiviral Agents Giant Cells Virus Cell Line law.invention Protein structure law Virology Animals Amino Acid Sequence Homology modeling Antiviral Homology model Syncytium Cell fusion virus diseases Lipid bilayer fusion respiratory system Fusion protein Molecular biology Respiratory Syncytial Viruses Mutation Recombinant DNA Binding Sites Antibody Sequence Alignment Viral Fusion Proteins |
| Zdroj: | Virology. 311:275-288 |
| ISSN: | 0042-6822 |
| DOI: | 10.1016/s0042-6822(03)00115-6 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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