This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chow, Y.-H. J. Articles by Palmarini, M. Search for Related Content PubMed PubMed Citation Articles by Chow, Y.-H. J. Articles by Palmarini, M.

Transformation of Rodent Fibroblasts by the Jaagsiekte Sheep Retrovirus Envelope Is Receptor Independent and Does Not Require the Surface Domain

Department of Medical Microbiology and Parasitology and Comparative Oncology Program, College of Veterinary Medicine, University of Georgia, Athens, Georgia 30602,¹ Istituto di Patologia Speciale e Clinica Medica Veterinaria, Universitá di Sassari, 07100 Sassari, Italy,² Department of Molecular Sciences, University of Tennessee Health Sciences Center, Memphis, Tennessee 38163³

Received 12 December 2002/ Accepted 26 February 2003

Jaagsiekte sheep retrovirus (JSRV) is the etiological agent of a contagious lung cancer of sheep known as ovine pulmonary adenocarcinoma (OPA). Expression of the JSRV envelope protein (Env) is sufficient to transform immortalized and primary fibroblasts, but the precise mechanisms of this process are not known. The cellular receptor for JSRV is hyaluronidase 2 (Hyal-2), the product of a putative tumor suppressor gene that in humans maps to a chromosomal region frequently deleted in the development of lung and breast cancers. Here we report studies to determine whether the Hyal-2-JSRV Env interaction plays a role in virus-induced transformation of rodent fibroblasts. Chimeric Env proteins between JSRV and the unrelated murine retroviruses Moloney murine leukemia virus (MMuLV) and mouse mammary tumor virus (MMTV) showed cell surface expression comparable to that of wild-type MMuLV Env and rescued infection of MMuLV particle pseudotypes. Interestingly, an MMuLV-JSRV chimera in which the putative receptor binding domain (RBD) and proline-rich region (PRR) of JSRV Env were replaced by the RBD and PRR of MMuLV induced transformation of 208F, a rodent fibroblast line. Cell lines derived from foci of MMuLV-JSRV chimera-transformed 208F cells grew in soft agar and showed Akt activation, a hallmark of JSRV-transformed rodent fibroblasts. Transformation assays performed using proteins with amino-terminal deletion mutations showed that the carboxy-terminal 141 amino acids of the transmembrane subunit (TM) were sufficient to induce cell transformation when targeted to the membrane with a myristoylation signal. Thus, the JSRV TM is necessary and sufficient to transform rodent fibroblasts. Taken together these results indicate that the interaction with Hyal-2 at least is not an essential determinant of JSRV-induced transformation of fibroblasts and that the viral TM functions essentially as an oncoprotein.

This article has been cited by other articles:

• Dunlap, K. A., Palmarini, M., Adelson, D. L., Spencer, T. E. (2005). Sheep Endogenous Betaretroviruses (enJSRVs) and the Hyaluronidase 2 (HYAL2) Receptor in the Ovine Uterus and Conceptus. Biol. Reprod. 73: 271-279 [Abstract] [Full Text]  
• Liu, S.-L., Miller, A. D. (2005). Transformation of Madin-Darby Canine Kidney Epithelial Cells by Sheep Retrovirus Envelope Proteins. J. Virol. 79: 927-933 [Abstract] [Full Text]  
• Hofacre, A., Fan, H. (2004). Multiple Domains of the Jaagsiekte Sheep Retrovirus Envelope Protein Are Required for Transformation of Rodent Fibroblasts. J. Virol. 78: 10479-10489 [Abstract] [Full Text]  
• Cousens, C., Bishop, J. V., Philbey, A. W., Gill, C. A., Palmarini, M., Carlson, J. O., DeMartini, J. C., Sharp, J. M. (2004). Analysis of Integration Sites of Jaagsiekte Sheep Retrovirus in Ovine Pulmonary Adenocarcinoma. J. Virol. 78: 8506-8512 [Abstract] [Full Text]  
• Palmarini, M., Mura, M., Spencer, T. E. (2004). Endogenous betaretroviruses of sheep: teaching new lessons in retroviral interference and adaptation. J. Gen. Virol. 85: 1-13 [Abstract] [Full Text]