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Journal of Virology, October 2004, p. 10479-10489, Vol. 78, No. 19
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.19.10479-10489.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Multiple Domains of the Jaagsiekte Sheep Retrovirus Envelope Protein Are Required for Transformation of Rodent Fibroblasts

Andrew Hofacre and Hung Fan*

Department of Molecular Biology and Biochemistry and Cancer Research Institute, University of California, Irvine, California

Received 9 December 2003/ Accepted 19 May 2004

Jaagsiekte sheep retrovirus (JSRV) is an exogenous retrovirus of sheep that induces a contagious lung cancer, ovine pulmonary adenocarcinoma. We previously showed that the gene encoding JSRV envelope protein (Env) appears to function as an oncogene, since it can transform mouse NIH 3T3 cells. The cytoplasmic tail of the Env transmembrane protein (TM) is necessary for the transformation. However, previous experiments did not exclude the involvement of the Env surface protein (SU) in transformation. In this study, we created a series of nested deletion mutants through the SU domain and assessed their ability to transform rodent fibroblasts. All SU deletion mutants downstream of the predicted signal peptide were unable to transform murine NIH 3T3 or rat 208F cells. Transport to the plasma membrane of selected deleted Env proteins was confirmed by confocal immunofluorescence microscopy of hemagglutinin-tagged versions. Additional sequential SU deletion mutants lacking 50-amino-acid (aa) blocks throughout SU also were unable to transform. Furthermore, minimal insertion mutants of two amino acids (Leu/Gln) at various positions in SU also abolished transformation. These data indicate that domains in SU facilitate efficient JSRV transformation. This could reflect a necessity of SU for appropriate configuration of the Env protein or independent activation by SU of a signaling pathway necessary for transformation. Complementation between SU and TM mutants for transformation supported the latter hypothesis. Cotransfection with {Delta}GP Y590F (mutant in the TM cytoplasmic tail) with {Delta}GP SU{Delta}103-352 (lacking most of SU) resulted in efficient transformation. The resulting transformants showed evidence for the presence and expression of both mutant plasmids.

* Corresponding author. Mailing address: Cancer Research Institute, Department of MB&B, University of California, Irvine, Irvine, CA 92697-3905. Phone: (949) 824-5554. Fax: (949) 824-4023. E-mail: hyfan{at}uci.edu.

Journal of Virology, October 2004, p. 10479-10489, Vol. 78, No. 19
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.19.10479-10489.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Nitta, T., Hofacre, A., Hull, S., Fan, H. (2009). Identification and Mutational Analysis of a Rej Response Element in Jaagsiekte Sheep Retrovirus RNA. J. Virol. 83: 12499-12511 [Abstract] [Full Text]  
  • Hofacre, A., Nitta, T., Fan, H. (2009). Jaagsiekte Sheep Retrovirus Encodes a Regulatory Factor, Rej, Required for Synthesis of Gag Protein. J. Virol. 83: 12483-12498 [Abstract] [Full Text]  
  • Hull, S., Fan, H. (2006). Mutational analysis of the cytoplasmic tail of jaagsiekte sheep retrovirus envelope protein.. J. Virol. 80: 8069-8080 [Abstract] [Full Text]  
  • Paul, T. A., Quackenbush, S. L., Sutton, C., Casey, R. N., Bowser, P. R., Casey, J. W. (2006). Identification and Characterization of an Exogenous Retrovirus from Atlantic Salmon Swim Bladder Sarcomas. J. Virol. 80: 2941-2948 [Abstract] [Full Text]  


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