Attenuate Newcastle disease virus by codon modification of the glycoproteins and phosphoprotein genes

• Published in: Virology (New York, N.Y.) Vol. 528; pp. 144 - 151
• Main Authors: Wang, Weijia, Cheng, Xing, Buske, Paul J., Suzich, JoAnn A., Jin, Hong
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2019
• Subjects: Attenuation; Codon modification; NDV; Newcastle disease virus; Oncolytic virus; Viral vector; NDV; Attenuation; Newcastle disease virus; Oncolytic virus; Viral vector; Codon modification
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2018.12.017

A codon modification strategy was used to attenuate the avian pathogenicity of an oncolytic mesogenic Newcastle disease virus (NDV) by targeting the three major virulence factors: the fusion (F) protein, hemagglutinin neuraminidase (HN) and phosphoprotein (P). Recoding the F and HN genes with rare codons greatly reduced expression of both F and HN proteins and resulted in their low incorporation into virions. The F and HN recoded virus was partially attenuated in chickens even when the F protein cleavage site was modified. Full attenuation was achieved when the 5′ portion of the P gene was recoded. The recoded P, F and HN triple gene mutant exhibited delayed cell death in human cancer cells with prolonged expression of a GFP transgene. While this engineered attenuated NDV strain has lower oncolytic potency, its capacity for prolonged transgene expression may allow its use as a vaccine or gene delivery vector.