Functional analysis of the short isoform of orf virus protein OV20.0
Journal
Journal of Virology
Journal Volume
89
Journal Issue
9
Pages
4966-4979
Date Issued
2015
Author(s)
Tseng, Yeu-Yang
Lin, Fong-Yuan
Cheng, Sun-Fang
Tscharke, David
Chulakasian, Songkhla
Chou, Chia-Chi
Liu, Ya-Fen
Chang, Wei-Shan
Wong, Min-Liang
Hsu, Wei-Li
Abstract
Orf virus (ORFV) OV20.0L is an ortholog of vaccinia virus (VACV) gene E3L. The function of VACV E3 protein as a virulence factor is well studied, but OV20.0 has received less attention. Here we show that like VACV E3L, OV20.0L encodes two proteins, a full-length protein and a shorter form (sh20). The shorter sh20 is an N-terminally truncated OV20.0 isoform generated when a downstream AUG codon is used for initiating translation. These isoforms differed in cellular localization, with full-length OV20.0 and sh20 found throughout the cell and predominantly in the cytoplasm, respectively. Nonetheless, both OV20.0 isoforms were able to bind double-stranded RNA (dsRNA)-activated protein kinase (PKR) and dsRNA. Moreover, both isoforms strongly inhibited PKR activation as shown by decreased phosphorylation of the translation initiation factor eIF2α subunit and protection of Sindbis virus infection against the activity of interferon (IFN). In spite of this apparent conservation of function in vitro, a recombinant ORFV that was able to express only the sh20 isoform was attenuated in a mouse model. ? 2015, American Society for Microbiology.
SDGs
Other Subjects
double stranded RNA; gamma interferon; initiation factor 2alpha; interferon; interleukin 6; isoprotein; OV20 0 protein; polyinosinic polycytidylic acid; protein kinase R; tumor necrosis factor alpha; unclassified drug; virus protein; DNA; E3L protein, Vaccinia virus; initiation factor 2; isoprotein; OV20.0L protein, Orf virus; protein binding; protein kinase R; RNA binding protein; virus protein; amino terminal sequence; animal cell; animal experiment; animal model; animal tissue; Article; cellular distribution; controlled study; cytokine production; cytokine response; cytoplasm; down regulation; enzyme activation; enzyme inhibition; female; human; human cell; in vitro study; in vivo study; mouse; nonhuman; Orf virus; priority journal; protein analysis; protein expression; protein function; protein localization; protein phosphorylation; protein protein interaction; protein RNA binding; Sindbis virus; togavirus infection; virus attenuation; virus pathogenesis; virus virulence; wild type; amino acid sequence; animal; antagonists and inhibitors; Bagg albino mouse; cell line; contagious ecthyma; disease model; genetics; metabolism; molecular genetics; Orf virus; pathology; phosphorylation; physiology; protein processing; sequence homology; virology; Orf virus; Sindbis virus; Vaccinia virus; Amino Acid Sequence; Animals; Cell Line; Disease Models, Animal; DNA; Ecthyma, Contagious; eIF-2 Kinase; Eukaryotic Initiation Factor-2; Humans; Mice, Inbred BALB C; Molecular Sequence Data; Orf virus; Phosphorylation; Protein Binding; Protein Isoforms; Protein Processing, Post-Translational; RNA-Binding Proteins; Sequence Homology, Amino Acid; Viral Proteins
Type
journal article