Advancements in the genomic feature of Newcastle disease virus and the multifaceted roles of non-structural proteins V/W in viral replication and pathogenesis.

As a prototype of paramyxovirus, Newcastle disease virus (NDV) is a highly contagious avian pathogen that usually causes substantial economic losses to the global poultry industry. Like other paramyxoviruses, the RNA genome of NDV can encode six structural proteins and two additional non-structural proteins (known as V and W proteins). The V and W proteins produced by the NDV P gene mRNA editing have been demonstrated to be major immune evasion factors antagonizing type I interferon antiviral response. In addition, the V and W proteins are also found to determine the virulence and pathotype of NDV, and affect viral replication and pathogenicity by interacting with multiple cellular proteins. Over the past 30 years, numerous studies have been made to reveal the potential biological functions of the NDV V/W proteins, but knowledge of the structure and function of the V/W proteins is less in-depth than that of other NDV proteins or most paramyxoviruses. Meanwhile, the information available for reference remains scattered and a systematic overview is lacking. Thus, this review comprehensively summarizes the advancements in the genome organization and P gene mRNA editing of NDV, as well as the structural features, virulence, and pathotype correlations of the NDV V/W proteins. Additionally, the crucial roles of V/W-cellular protein interactions in NDV replication and pathogenicity are discussed. Finally, the future research directions and main challenges are briefly summarized. This review offers valuable insights for understanding the unclear replication and pathogenesis of NDV and developing intervention strategies to control the infection of NDV and related paramyxoviruses.