Jaagsiekte sheep retrovirus (JSRV) is the causative agent of ovine pulmonary adenocarcinoma (OPA), a transmissible lung cancer in sheep (14). JSRV induces tumors rapidly under experimental conditions (28), and we previously showed that the JSRV envelope protein functions as an oncogene, in that it can morphologically transform mouse NIH 3T3 and rat Rat 208F fibroblasts in vitro (24, 34). The mechanism(s) by which JSRV Env can cause cell transformation is of great interest. We also previously showed that the cytoplasmic tail of the envelope transmembrane (TM) protein is necessary for fibroblast transformation (29). In particular, a putative docking site for phosphatidylinositol 3-kinase (PI3K) in the cytoplasmic tail was implicated, because mutations in this motif (YXXM) eliminated transformation. On the other hand, we subsequently found that disabling PI3K signaling in cells does not prevent JSRV transformation, although in such cells the downstream effector molecule Akt/protein kinase B (PKB) was still phosphorylated (25). Also, Akt is not absolutely required for JSRV transformation of chicken embryo fibroblasts (40). Thus, the role of the PI3K-Akt pathway in JSRV transformation is unclear, although downstream parts of the pathway in particular might be involved.Akt is known to phosphorylate several downstream substrates that are involved in several signaling pathways associated with human cancers (5). Phosphorylation substrates of Akt include glycogen synthase kinase 3 (GSK-3), the Forkhead transcription factor, the proapoptotic Bad protein, and the mammalian target of rapamycin (mTOR). Akt phosphorylation of GSK-3␤, Forkhead, and Bad inactivates these proteins, while phosphorylation of mTOR activates it. In particular, the mammalian target of rapamycin (mTOR) [SEP]) is a 289-kDa serine/threonine kinase that is an ortholog of the Saccharomyces cerevisiae target of rapamycin 1 (TOR1) and TOR2 (8,35). mTOR is a key regulator of cell growth and division at the level of translation (17) by activating (phosphorylating) p70 S6 kinase and phosphorylating (inactivating) 4EBP1, a negative regulatory binding protein of translation initiation factor eIF4G (32). The mTOR inhibitor rapamycin was first identified as an antifungal agent (36, 37). Its specificity

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The complete genome sequence of a new isolate of enzootic nasal tumour virus (ENTV-2), associated with enzootic nasal adenocarcinoma (ENA) of goats, was determined. The genome exhibits a genetic organization characteristic of b-retroviruses. ENTV-2 is closely related to the retrovirus (ENTV-1) associated with enzootic adenocarcinoma of sheep, and to jaagsiekte retrovirus. The main sequence differences between these viruses reside in orfX, the U3 LTR, two small regions in gag and the transmembrane (TM) region of env. Sequence analysis of the TM region of env from several sheep and goats naturally affected by ENA suggested that ENTV-1 and ENTV-2 are distinct viruses rather than geographical variants. Although both viruses transform secretory epithelial cells of the ethmoid turbinate, the study of their tissue distribution using specific PCRs showed that ENTV-2 establishes a disseminated lymphoid infection whereas ENTV-1 is mainly confined to the tumour.

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