1887

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, and is activated by proteolytic cleavage between amino acids 116 and 117 to produce two disulfide-linked subunits, F and F. The consensus sequence of the F protein cleavage site of virulent [(R/K)-R-Q-(R/K)-R↓F-I] and avirulent [(G/E)-(K/R)-Q-(G/E)-R↓L-I] 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.

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2011-10-01
2024-04-25
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