Comparative biology of two genetically closely related Newcastle disease virus strains with strongly contrasting pathogenicity

A lentogenic strain of Newcastle disease virus (NDV) with an intracerebral pathogenicity index (ICPI) of 0.36 was derived by the passage of a mesogenic NDV isolate with an original ICPI of 1.04. Animal experiments showed that the original strain caused much severer clinical signs and mortality than the derived strain in chickens. To elucidate the molecular reason for this virulence change, the complete viral genomes of the original and derived strains were sequenced. Molecular analysis showed that both viruses contained the same fusion (F) protein with a cleavage site (Fcs) motif that is usually associated with velogenic viruses. Molecular comparison revealed five amino acid (aa) differences in nucleoprotein (NP) (aa 426), hemagglutinin-neuraminidase (HN) (aas 215 and 430), and large protein (L) (aas 1694 and 1767), accompanied by the changes of relevant biological activities in membrane fusion and replication. Thus, we believe that the virulence changes may induced by these mutations. Our findings make a foundation for more in-depth investigations of the molecular mechanism underlying virulence.