The Role of Dual Mutations G347E and E349D of the Pigeon Paramyxovirus Type 1 Hemagglutinin-Neuraminidase Protein In Vitro and In Vivo

• Published in: Veterinary sciences 2024-11, Vol.11 (12), p.592
• Main Authors: Chen, Yu, Gong, Junhao, Zhan, Tiansong, Wang, Mingzhan, Hu, Shunlin, Liu, Xiufan
• Format: Article
• Language: English
• Subjects: Affinity; Amino acids; antigenic variation; Aspartate; Aspartic acid; Birds; China; Committees; cross-species transmission; Diseases; Embryos; Epidemics; Exo-a-sialidase; Fibroblasts; Genetic aspects; Genotype & phenotype; Glutamic acid; Glycine; Health aspects; Hemagglutinins; HN protein; Infections; Infectious diseases; Infectivity; Laboratory animals; Lectins; Mutation; Newcastle disease; Northwest Territories; Pathogenicity; pigeon ND; Plasmids; Poultry; PPMV-1; Proteins; Replication; RNA polymerase; Vaccines; Viral infections; Virulence; Viruses
• ISSN: 2306-7381; 2306-7381
• DOI: 10.3390/vetsci11120592

Pigeon Newcastle disease (ND) is the most common viral infectious disease in the pigeon industry, caused by pigeon paramyxovirus type 1 (PPMV-1), a variant of chicken-origin Newcastle disease virus (NDV). Previous studies have identified significant amino acid differences between PPMV-1 and chicken-origin NDV at positions 347 and 349 in the hemagglutinin-neuraminidase (HN) protein, with PPMV-1 predominantly exhibiting glycine (G) at position 347 and glutamic acid (E) at position 349, while most chicken-origin NDVs show E at position 347 and aspartic acid (D) at position 349. However, the impact of these amino acid substitutions remains unclear. In this study, we generated a recombinant virus, NT-10-G347E/E349D, by introducing the G347E and E349D dual mutations into a PPMV-1 strain NT-10 using reverse genetics. The biological characteristics of NT-10 and NT-10-G347E/E349D were compared both in vitro and in vivo. In vitro, the G347E and E349D dual mutations reduce NT-10's replication and neuraminidase activity in pigeon embryo fibroblast (PEF) cells while enhancing both in chicken embryo fibroblast (CEF) cells. Additionally, these mutations decrease NT-10's binding affinity to the α-2,6 sialic acid receptor while significantly increasing its affinity for the α-2,3 receptor. In vivo, NT-10-G347E/E349D exhibited reduced pathogenicity in pigeons but increased pathogenicity in chickens compared to the parental NT-10 strain. The mutations also reduced the pigeon-to-pigeon transmission of NT-10 but enhanced its transmission from pigeons to chickens. Notably, significant antigenic differences were observed between NT-10 and NT-10-G347E/E349D, as an inactivated vaccine based on NT-10 provided full protection against NT-10 challenge in immunized pigeons but only 67% mortality protection against NT-10-G347E/E349D. Overall, these findings underscore the critical role of amino acids at positions 347 and 349 in PPMV-1 infection, pathogenicity, and transmission, providing a theoretical foundation for the scientific prevention and control of PPMV-1.