1887

Abstract

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 , and , WDSV contains three open reading frames (ORFs), designated , and . is located between the 5′ long terminal repeat and . Developing tumours contain low levels of and 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 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.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.18570-0
2003-02-01
2020-05-26
Loading full text...

Full text loading...

/deliver/fulltext/jgv/84/2/vir840375.html?itemId=/content/journal/jgv/10.1099/vir.0.18570-0&mimeType=html&fmt=ahah

References

  1. Andersson P., Goldfarb M. P., Weinberg R. A.. 1979; A defined subgenomic fragment of in vitro synthesized Moloney sarcoma virus DNA can induce cell transformation upon transfection. Cell16:63–75
    [Google Scholar]
  2. Bowser P. R., Wolfe M. J., Forney J. L., Wooster G. A.. 1988; Seasonal prevalence of skin tumors from walleye ( Stizostedion vitreum ) from Oneida Lake. New York. J Wildl Dis24:292–298
    [Google Scholar]
  3. Bowser P. R., Martineau D., Wooster G. A.. 1990; Effects of water temperature on experimental transmission of dermal sarcoma in fingerling walleyes ( Stizostedion vitreum ). J Aquat Anim Health2:157–161
    [Google Scholar]
  4. Bowser P. R., Wooster G. A., Quackenbush S. L., Casey R. N., Casey J. W.. 1996; Comparison of fall and spring tumors as inocula for experimental transmission of walleye dermal sarcoma. J Aquat Anim Health8:78–81
    [Google Scholar]
  5. Boya P., Roques B., Kroemer G.. 2001; Viral and bacterial proteins regulating apoptosis at the mitochondrial level. EMBO J20:4325–4331
    [Google Scholar]
  6. Chen H.-C., Appeddu P. A., Isoda H., Guan J.-L.. 1996; Phosphorylation of tyrosine 397 in focal adhesion kinase is required for binding phosphatidylinositol 3-kinase. J Biol Chem271:26329–26334
    [Google Scholar]
  7. Ciminale V., Zotti L., D'Agostino D. M., Ferro T., Casareto L., Franchini G., Bernardi P., Chieco-Bianchi L.. 1999; Mitochondrial targeting of the p13II protein coded by the x-II ORF of human T-cell leukemia/lymphotropic virus type I (HTLV-I). Oncogene18:4505–4514
    [Google Scholar]
  8. Copeland N. G., Cooper G. M.. 1979; Transfection by exogenous and endogenous murine retrovirus DNAs. Cell16:347–356
    [Google Scholar]
  9. De Vos K., Goossens V., Boone E., Vercammen D., Vancompernolle K., Vandenabeele P., Haegeman G., Fiers W., Grooten J.. 1998; The 55-kDa tumor necrosis factor receptor induces clustering of mitochondria through its membrane-proximal region. J Biol Chem273:9673–9680
    [Google Scholar]
  10. De Vos K., Severin F., Van Herreweghe F., Vancompernolle K., Goossens V., Hyman A., Grooten J.. 2000; Tumor necrosis factor induces hyperphosphorylation of kinesin light chain and inhibits kinesin-mediated transport of mitochondria. J Cell Biol149:1207–1214
    [Google Scholar]
  11. Emanuelsson O., Nielsen H., Brunak S., von Heijne G.. 2000; Predicting subcellular localization of proteins based on their N-terminal amino acid sequence. J Mol Biol300:1005–1016
    [Google Scholar]
  12. Gey G. O., Coffman W. D., Kubicek M. T.. 1952; Tissue culture studies of the proliferative capacity of cervical carcinoma and normal epithelium. Cancer Res12:264–265
    [Google Scholar]
  13. Holzschu D. L., Martineau D., Fodor S. K., Vogt V. M., Bowser P. R., Casey J. W.. 1995; Nucleotide sequence and protein analysis of a complex piscine retrovirus, walleye dermal sarcoma virus. J Virol69:5320–5331
    [Google Scholar]
  14. Jacotot E., Ravagnan L., Loeffler M.. 15 other authors 2000; The HIV-1 viral protein R induces apoptosis via a direct effect on the mitochondrial permeability transition pore. J Exp Med191:33–46
    [Google Scholar]
  15. Jacotot E., Ferri K. F., El Hamel C.. 17 other authors 2001; Control of mitochondrial membrane permeabilization by adenine nucleotide translocator interacting with HIV-1 viral protein rR and Bcl-2. J Exp Med193:509–519
    [Google Scholar]
  16. Jainchill J. L., Aaronson S. A., Todaro G. J.. 1969; Murine sarcoma and leukemia viruses: assay using clonal lines of contact-inhibited mouse cells. J Virol4:549–553
    [Google Scholar]
  17. Lairmore M. D., Stanley J. R., Weber S. A., Holzschu D. L.. 2000; Squamous epithelial proliferation induced by walleye dermal sarcoma retrovirus cyclin in transgenic mice. Proc Natl Acad Sci U S A97:6114–6119
    [Google Scholar]
  18. LaPierre L. A., Casey J. W., Holzschu D. L.. 1998; Walleye retroviruses associated with skin tumors and hyperplasias encode cyclin D homologs. J Virol72:8765–8771
    [Google Scholar]
  19. LaPierre L. A., Holzschu D. L., Bowser P. R., Casey J. W.. 1999; Sequence and transcriptional analyses of the fish retroviruses walleye epidermal hyperplasia virus types 1 and 2: evidence for a gene duplication. J Virol73:9393–9403
    [Google Scholar]
  20. Martineau D., Bowser P. R., Wooster G. A., Armstrong L. D.. 1990a; Experimental transmission of a dermal sarcoma in fingerling walleyes ( Stizostedion vitreum vitreum . Vet Pathol27:230–234
    [Google Scholar]
  21. Martineau D., Bowser P. R., Wooster G. A., Forney J. L.. 1990b; Histologic and ultrastructural studies of dermal sarcoma of walleye (Pisces: Stizostedion vitreum . Vet Pathol27:340–346
    [Google Scholar]
  22. Martineau D., Renshaw R., Williams J. R., Casey J. W., Bowser P. R.. 1991; A large unintegrated retrovirus DNA species present in a dermal tumor of walleye Stizostedion vitreum . Dis Aquat Org10:153–158
    [Google Scholar]
  23. Martineau D., Bowser P. R., Renshaw R. R., Casey J. W.. 1992; Molecular characterization of a unique retrovirus associated with a fish tumor. J Virol66:596–599
    [Google Scholar]
  24. Mattingly R. R., Sorisky A., Brann M. R., Macara I. G.. 1994; Muscarinic receptors transform NIH 3T3 cells through a Ras-dependent signalling pathway inhibited by the Ras-GTPase-activating protein SH3 domain. Mol Cell Biol14:7943–7952
    [Google Scholar]
  25. Nelson-Rees W. A., Owens R. B., Arnstein P., Kniazeff A. J.. 1976; Source, alterations, characteristics and use of a new dog cell line (Cf2Th). In Vitro12:665–669
    [Google Scholar]
  26. Quackenbush S. L., Holzschu D. L., Bowser P. R., Casey J. W.. 1997; Transcriptional analysis of walleye dermal sarcoma virus (WDSV). Virology237:107–112
    [Google Scholar]
  27. Rahmani Z., Huh K.-W., Lasher R., Siddiqui A.. 2000; Hepatitis B virus X protein colocalizes to mitochondria with a human voltage-dependent anion channel, HVDAC3, and alters its transmembrane potential. J Virol74:2840–2846
    [Google Scholar]
  28. Rovnak J., Casey J. W., Quackenbush S. L.. 2001; Intracellular targeting of walleye dermal sarcoma virus Orf A (rv-cyclin). Virology280:31–40
    [Google Scholar]
  29. Takada S., Shirakata Y., Kaneniwa N., Koike K.. 1999; Association of hepatitis B virus X protein with mitochondria causes mitochondrial aggregation at the nuclear periphery, leading to cell death. Oncogene18:6965–6973
    [Google Scholar]
  30. Walker R.. 1969; Virus associated with epidermal hyperplasia in fish. Natl Cancer Inst Monogr31:195–207
    [Google Scholar]
  31. Wolf K., Mann J. A.. 1980; Poikilotherm vertebrate cell lines and viruses: a current listing for fishes. Fish Dis Diagn16:168–179
    [Google Scholar]
  32. Yamamoto T., MacDonald R. D., Gillespie D. C., Kelly R. K.. 1976; Viruses associated with lymphocystis and dermal sarcoma of walleye ( Stizostedion vitreum vitreum ). J Fish Res Board Can33:2408–2419
    [Google Scholar]
  33. Yamamoto T., Kelly R. K., Nielsen O.. 1985; Morphological differentiation of virus-associated skin tumors of walleye ( Stizostedion vitreum vitreum ). Fish Pathol20:361–372
    [Google Scholar]
  34. Zhang Z., Martineau D.. 1999; Walleye dermal sarcoma virus: OrfA N-terminal end inhibits the activity of a reporter gene directed by eukaryotic promoters and has a negative effect on the growth of fish and mammalian cells. J Virol73:8884–8889
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.18570-0
Loading
/content/journal/jgv/10.1099/vir.0.18570-0
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error