title: LaSota fusion (F) cleavage motif-mediated fusion activity is affected by other regions of the F protein from different genotype Newcastle disease virus in a chimeric virus: implication for virulence attenuation.
abstract: The cleavage site sequence of the fusion (F) protein contributes to a wide range of virulence of Newcastle disease virus (NDV). In this study, we identified other important amino acid sequences of the F protein that affect cleavage and modulation of fusion. We generated chimeric Beaudette C (BC) viruses containing the cleavage site sequence of avirulent strain LaSota (Las-Fc) together with various regions of the F protein of another virulent strain AKO. We found that the F1 subunit is important for cleavage inhibition. Further dissection of the F1 subunit showed that replacement of four amino acids in the BC/Las-Fc protein with their AKO counterparts (T341S, M384I, T385A and I386L) resulted in an increase in fusion and replication in vitro. In contrast, the mutation N403D greatly reduced cleavage and viral replication, and affected protein conformation. These findings will be useful in developing improved live NDV vaccines and vaccine vectors.
authors.affiliation: Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, 8075 Greenmead Drive, College Park, MD 20742, USA.
authors.forename: Shin-Hee
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, 8075 Greenmead Drive, College Park, MD 20742, USA.
authors.forename: Sa
authors.initials: S
authors.lastname: Xiao
authors.affiliation: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Collins
authors.affiliation: Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, 8075 Greenmead Drive, College Park, MD 20742, USA.
authors.forename: Siba K
authors.initials: SK
authors.lastname: Samal
mesh_terms: D000818:Animals; D002460:Cell Line; D002645:Chickens; D003588:Cytopathogenic Effect, Viral; D009522:Newcastle disease virus / Q000235:genetics* / Q000502:physiology*; D011995:Recombination, Genetic; D014760:Viral Fusion Proteins / Q000235:genetics* / Q000378:metabolism*; D014774:Virulence; D053586:Virus Internalization; D014779:Virus Replication
chemical_list: D014760:Viral Fusion Proteins