Insights into the multifunctionality of viral glycoproteins F and HN in the lifecycle and pathogenesis of Newcastle disease virus: a systematic review.

Newcastle disease virus (NDV) is a representative paramyxovirus that usually causes severe infections and substantial economic losses to the global poultry industry. Over the years, NDV has attracted widespread attention as a promising oncolytic virotherapy agent and vector vaccine against many pathogens and an important prototype for elucidating the replication and pathogenesis of other paramyxoviruses. The F and HN glycoproteins are two kinds of glycosylated transmembrane proteins located on the virion envelope that play multiple roles in the virulence, infection, replication, and pathogenicity of NDV. In view of the ability to induce neutralizing and protective antibodies and the similarity in the structural features of the F and HN glycoproteins of NDV and other paramyxoviruses, investigating their structures and functions is beneficial for understanding the viral lifecycle and pathogenesis and developing more effective broad-spectrum antibodies or antiviral drugs against viral infection. This systematic review aims to summarize the structural features and membrane fusion mechanism of the F and HN glycoproteins and their relationships with viral virulence, pathogenic phenotype and thermostability, coupled with the crucial roles of F/HN-host protein/compound interactions in the infection, replication, and pathogenicity of NDV. Additionally, this review also highlights the importance of technologies such as protein‒protein interactome analysis, single-particle cryo-electron microscopy, genome-wide CRISPR/Cas9 library screening, and computational structural biology for providing novel viewpoints on the lifecycle and pathogenesis of NDV and related paramyxoviruses and valuable reference information for the future development of efficient treatment strategies targeting viral glycoproteins.