Walleye dermal sarcoma virus Orf C is targeted to the mitochondria

• Published in: Journal of general virology 2003-02, Vol.84 (2), p.375-381
• Main Authors: Nudson, Wade A, Rovnak, Joel, Buechner, Matthew, Quackenbush, Sandra L
• Format: Article
• Language: English
• Subjects: Animals; Cell Line; Dogs; Epsilonretrovirus - pathogenicity; Fish Diseases - metabolism; Fish Diseases - virology; Fishes - virology; Humans; Marine; Mice; Mitochondria - metabolism; Retroviridae Infections - metabolism; Retroviridae Infections - veterinary; Retroviridae Infections - virology; Retroviridae Proteins - genetics; Retroviridae Proteins - metabolism; Retrovirus; Sarcoma - veterinary; Sarcoma - virology; Skin Neoplasms - veterinary; Skin Neoplasms - virology; Tumor Virus Infections - metabolism; Tumor Virus Infections - veterinary; Tumor Virus Infections - virology; Walleye dermal sarcoma virus
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/vir.0.18570-0

Department of Molecular Biosciences, University of Kansas, 7047 Haworth Hall, 1200 Sunnyside Avenue, Lawrence, KS 66045-7534, USA Correspondence Sandra Quackenbush squack{at}ku.edu Walleye dermal sarcomas are associated with the presence of a complex retrovirus, walleye dermal sarcoma virus (WDSV). These sarcomas develop and regress seasonally in naturally infected fish. In addition to gag , pol and env , WDSV contains three open reading frames (ORFs), designated orf a , orf b and orf c . orf c is located between the 5' long terminal repeat and gag . Developing tumours contain low levels of orf a and orf b transcripts, whereas regressing tumours contain high levels of genomic transcripts and virus particles. Orf C protein is encoded by the full-length, genomic transcript and can be detected in tumour extracts with anti-Orf C-specific antisera. To determine the subcellular location of WDSV Orf C, cultured cells were transfected with an expression vector encoding haemagglutinin-tagged Orf C and examined by immunofluorescence. Orf C was observed throughout the cytoplasm and accumulated in cytoplasmic organelles. Dual-antibody staining for Orf C and mitochondrial cytochrome c demonstrated colocalization of Orf C with mitochondria and loss of the normal distribution of mitochondria in the cytoplasm. Cells transiently expressing Orf C exhibited apoptotic morphology and increased levels of surface phosphatidylserine and were unable to retain MitoTracker Orange, a dye that accumulates in active mitochondria. These results imply a functional role for WDSV Orf C in an alteration of mitochondrial function that results in apoptosis contributing to tumour regression. Present address: Stowers Institute for Medical Research, Kansas City, MO, USA.