title: A single amino acid change, Q114R, in the cleavage-site sequence of Newcastle disease virus fusion protein attenuates viral replication and pathogenicity.
abstract: A key determinant of Newcastle disease virus (NDV) virulence is the amino acid sequence at the fusion (F) protein cleavage site. The NDV F protein is synthesized as an inactive precursor, F(0), and is activated by proteolytic cleavage between amino acids 116 and 117 to produce two disulfide-linked subunits, F(1) and F(2). The consensus sequence of the F protein cleavage site of virulent [(112)(R/K)-R-Q-(R/K)-R↓F-I(118)] and avirulent [(112)(G/E)-(K/R)-Q-(G/E)-R↓L-I(118)] strains contains a conserved glutamine residue at position 114. Recently, some NDV strains from Africa and Madagascar were isolated from healthy birds and have been reported to contain five basic residues (R-R-R-K-R↓F-I/V or R-R-R-R-R↓F-I/V) at the F protein cleavage site. In this study, we have evaluated the role of this conserved glutamine residue in the replication and pathogenicity of NDV by using the moderately pathogenic Beaudette C strain and by making Q114R, K115R and I118V mutants of the F protein in this strain. Our results showed that changing the glutamine to a basic arginine residue reduced viral replication and attenuated the pathogenicity of the virus in chickens. The pathogenicity was further reduced when the isoleucine at position 118 was substituted for valine.
authors.affiliation: Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, MD 20742, USA.
authors.forename: Sweety
authors.initials: S
authors.lastname: Samal
authors.affiliation: Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, MD 20742, USA.
authors.forename: Sachin
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, MD 20742, USA.
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Khattar
authors.affiliation: Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, MD 20742, USA.
authors.forename: Siba K
authors.initials: SK
authors.lastname: Samal
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics*; D000818:Animals; D002645:Chickens; D016297:Mutagenesis, Site-Directed; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D020125:Mutation, Missense; D009521:Newcastle Disease / Q000473:pathology / Q000821:virology; D009522:Newcastle disease virus / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity*; D011201:Poultry Diseases / Q000473:pathology / Q000821:virology; D014760:Viral Fusion Proteins / Q000235:genetics* / Q000378:metabolism*; D014774:Virulence; D014779:Virus Replication
chemical_list: D050505:Mutant Proteins; D014760:Viral Fusion Proteins