RT info:eu-repo/semantics/article
T1 Mutations in the Ectodomain of Newcastle Disease Virus Fusion Protein Confer a Hemagglutinin-Neuraminidase-Independent Phenotype
A1 Ayllón Barasoain, Juan
A1 Villar, Enrique
A1 Muñoz Barroso, Isabel
K1 Bioquímica
K1 Biochemistry
K1 Biología molecular
K1 Molecular biology
AB The entry of enveloped viruses into host cells is preceded by membrane fusion, which in paramyxoviruses istriggered by the fusion (F) protein. Refolding of the F protein from a metastable conformation to a highly stablepostfusion form is critical for the promotion of fusion, although the mechanism is still not well understood.Here we examined the effects of mutations of individual residues of the F protein of Newcastle disease virus,located at critical regions of the protein, such as the C terminus of the N-terminal heptad repeat (HRA) andthe N terminus of the C-terminal heptad repeat (HRB). Seven of the mutants were expressed at the cell surface,showing differences in antibody reactivity in comparison with the F wild type. The N211A, L461A, I463A, andI463F mutants showed a hyperfusogenic phenotype both in syncytium and in dye transfer assays. The fourmutants promoted fusion more efficiently at lower temperatures than the wild type did, meaning they probablyhad lower energy requirements for activation. Moreover, the N211A, I463A, and I463F mutants exhibitedhemagglutinin-neuraminidase (HN)-independent activity when influenza virus hemagglutinin (HA) was coexpressed as an attachment protein. The data are discussed in terms of alterations of the refolding pathwayand/or the stability of the prefusion and fusion conformations.
PB American Society for Microbiology
SN 0022-538X
YR 2010
FD 2010-01
LK http://hdl.handle.net/10259/8376
UL http://hdl.handle.net/10259/8376
LA eng
NO This work was partially supported by grants from Junta de Castilla y León (SA009A08) to I.M.-B. and from Fondo de Investigaciones Sanitarias (FIS) (PI08/1813) to E.V. J.A. is a predoctoral fellowship holder from the Spanish Ministerio de Educacio´n, Cultura y Deportes (FPU program; AP-2004-6065). We thank Adolfo García-Sastre for providing anti-HN and polyclonal anti-NDV. Thanks are also due to N. Skinner for language corrections.
DS Repositorio Institucional de la Universidad de Burgos
RD 12-may-2024