Newcastle Disease Virus Fusion and Haemagglutinin-Neuraminidase Gene Divergence: Implications for Vaccines

Avian orthoavulavirus 1 (AOaV-1), commonly known as Newcastle disease virus (NDV), despite widespread vaccination, remains a significant threat to domestic chickens (Gallus gallus domesticus). Currently available live-attenuated NDV vaccines are derived from genotypes I and II lentogenic strains, whereas genetically divergent velogenic strains predominantly caused recent NDV outbreaks. This study examined the extent of genotypic divergence between NDV vaccine strains and field strains using phylogenetic and multivariate analyses of two major antigenic and virulence-associated genes: fusion (F) and haemagglutinin-neuraminidase (HN). A total of 121 full-length NDV-F and 81 NDV-HN gene sequences, representing reported NDV genotypes, were downloaded from GenBank and analysed using maximum-likelihood (ML) phylogenetic trees and principal coordinates analysis (PCoA). The phylogeny revealed genotype-specific clustering for both genes, consistent with current NDV classification. NDV vaccine strains belonging to genotypes I and II formed distinct clades, segregated from the majority of NDV field strains, including velogenic or virulent NDV genotypes. The principal coordinates analysis of both genes further confirmed the phylogenetic clustering of NDV genotypes, indicating increased genomic heterogeneity. These findings suggest genetic segregation of divergent velogenic or virulent genotypes from lentogenic NDV vaccines, requiring biological experiments for determining their efficacy against field strains. This study highlights the importance of molecular surveillance of NDV to monitor its genomic diversity, which is crucial for developing strategies to combat NDV outbreaks in domestic chickens. This study provides an updated, NDV-glycoprotein-gene-based comparative analysis across reported NDV genotypes using phylogenetic and multivariate approaches.