A genetically-distinct Pigeon Paramyxovirus-I isolate fails to cross-react with neutralizing antibodies raised by...

Pigeon paramyxovirus-1 (PPMV-1) is a major cause of mortality in domestic and free-living pigeons worldwide and has the potential to infect chickens, posing risks to the poultry sector. This study investigated a severe outbreak of PPMV-1 in a racing pigeon loft in Srinagar, India, despite routine vaccination with the LaSota strain. Molecular screening of 30 clinical samples identified NDV in 18 birds by real-time qPCR targeting the matrix gene. Histopathology revealed characteristic viscerotropic lesions, including epithelial necrosis and congestion in the proventriculus and duodenum, sinusoidal dilation in the liver, and lymphoid depletion in the spleen, consistent with pathogenic NDV infection. Whole genome sequencing of one of the isolates FVSC-S64 showed a virulent multi-basic cleavage site motif (113-KRQKRF-117) and classified the strain as genotype XXI.1.2. Phylogenetic analysis demonstrated close clustering with pigeon-derived isolates from Pakistan and Eastern Europe, while showing marked genetic divergence from Class I and other Class II strains. Comparative analysis revealed extensive amino acid substitutions within major antigenic regions of the fusion protein, including L69M (A1-A3) and Y337H, T341S, and R349K (A5), along with substitutions in antigenic regions of the hemagglutinin-neuraminidase protein, notably D349S and G494D. Virus neutralization testing showed that sera from LaSota-vaccinated chicken developed strong homologous neutralizing responses but failed to neutralize the FVSC-S64 isolate, demonstrating a pronounced antigenic mismatch. Together, these molecular, pathological, and serological findings provide clear evidence of vaccine escape by an emergent genotype XXI.1.2 PPMV-1 strain and highlight the urgent need for genotype-matched vaccines to improve NDV control in pigeon populations.