The W195 Residue of the Newcastle Disease Virus V Protein Is Critical for Multiple Aspects of Viral Self-Regulation through Interactions between V and Nucleoproteins

Author:

Wei Qiaolin1,Wang Wenbin2,Meng Fanxing1,Wang Ying1,Wei Ning1,Tian Jianxia1,Li Hanlue1ORCID,Hao Qiqi1,Zhou Zijie1,Liu Haijin1,Yang Zengqi1,Xiao Sa1

Affiliation:

1. College of Veterinary Medicine, Northwest A&F University, Yangling, Xianyang 712100, China

2. Poultry Institute, Shandong Academy of Agricultural Science, Jinan 250100, China

Abstract

The transcription and replication of the Newcastle disease virus (NDV) strictly rely on the viral ribonucleoprotein (RNP) complex, which is composed of viral NP, P, L and RNA. However, it is not known whether other viral non-RNP proteins participate in this process for viral self-regulation. In this study, we used a minigenome (MG) system to identify the regulatory role of the viral non-RNP proteins V, M, W, F and HN. Among them, V significantly reduced MG-encoded reporter activity compared with the other proteins and inhibited the synthesis of viral mRNA and cRNA. Further, V interacted with NP. A mutation in residue W195 of V diminished V–NP interaction and inhibited inclusion body (IB) formation in NP-P-L-cotransfected cells. Furthermore, a reverse-genetics system for the highly virulent strain F48E9 was established. The mutant rF48E9-VW195R increased viral replication and apparently enhanced IB formation. In vivo experiments demonstrated that rF48E9-VW195R decreased virulence and retarded time of death. Overall, the results indicate that the V–NP interaction of the W195 mutant V decreased, which regulated viral RNA synthesis, IB formation, viral replication and pathogenicity. This study provides insight into the self-regulation of non-RNP proteins in paramyxoviruses.

Funder

National Natural Science Foundation of China

Publisher

MDPI AG

Reference41 articles.

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