C-terminal 20 residues of ORF3 protein of duck circovirus genotype 2 regulates the nuclear localization and inhibits apoptotic activity of ORF3 protein

• Published in: Veterinary microbiology 2018-02, Vol.214, p.21-27
• Main Authors: Wu, Zhuan-Chang, Zhang, Rui-Hua, Li, Yu-Ming, Shao, Dong-Hua, Chen, Hua, Jiang, Shi-Jin, Ma, Zhi-Yong, Wang, Xin
• Format: Article
• Language: English
• Subjects: Animal diseases; Apoptosis; Aquatic birds; C-Terminus; Duck circovirus; Genotype & phenotype; Genotypes; Localization; Nonsense mutation; Nuclear localization signal; ORF3; Orf3 gene; Point mutation; Proteins; Residues; Stop codon; Viral infections; Virology; Wildfowl
• ISSN: 0378-1135; 1873-2542
• DOI: 10.1016/j.vetmic.2017.12.002

•A T236A mutation in ORF3 gene of DuCV genotype 1 strains resulted in a premature stop codon and 20 aa shorter at its C-terminus than the ORF3 protein of DuCV genotype 2 strains.•A NLS (RRLRTCNCRACRTLK) was identified within the C-terminal region of the ORF3 protein of DuCV genotype 2, which was essential for the nuclear localization of ORF3 protein.•The C-terminal 20 residues of the ORF3 protein of DuCV genotype 2 inhibited the apoptotic activity of DuCV ORF3 protein. Duck circovirus (DuCV) is divided into genotypes 1 and 2. The DuCV ORF3 protein is a newly identified viral protein with apoptotic activity. In this study, the differences in the gene sequences, subcellular localization, and apoptotic activities of the ORF3 proteins of DuCV genotypes 1 and 2 were analyzed. A T-to-A point mutation at nucleotide 236 (T236A) in the ORF3 gene sequence of DuCV genotype 1 was observed, which generates a premature stop codon (TAG) and resulted in a truncated ORF3 protein. The ORF3 protein of DuCV genotype 2 is 20 amino acids longer at its C-terminus than the truncated ORF3 protein of genotype 1. A variant monopartite-type nuclear localization signal (RRLRTCNCRACRTLK) was identified within the C-terminal region of the ORF3 protein of DuCV genotype 2, which is essential for the nuclear localization of the protein. The 20 C-terminal residues of the DuCV genotype 2 ORF3 protein also inhibits the apoptotic activity of the protein. Our findings provide insight into the biological and functional characteristics of the DuCV ORF3 protein.