Genomic characterization of genotype IV Newcastle disease virus isolates
Class II genotype IV Newcastle disease virus (NDV), historically responsible for the first ND panzootic in the mid-20th century, was presumed extinct after its last detection in 2000. This study reports the re-emergence of four virulent genotype IV NDV isolates from 6,731 wild and domestic birds sampled across nine provinces of China between 2021 and 2023. Phylogenetic and molecular analyses revealed that these isolates belong to subgenotype IVa and exhibit remarkable genetic stability, showing > 99 % identity to ancestral strains isolated in the 1930s–1970s. The representative isolate KS02 caused rapid lethality and efficient transmission in specific-pathogen-free chicks, surpassing the virulence of a genotype VII reference strain. LaSota vaccination at the conventional hemagglutination-inhibition (HI) threshold provided only partial protection (55 % survival) but achieved complete protection when HI titers were at least twofold higher. These findings indicate that re-emerged genotype IV NDV maintains strong virulence with limited vaccine cross-protection, underscoring the need for enhanced surveillance and updated vaccination strategies along East Asian migratory flyways.