Jaagsiekte Sheep Retrovirus

Jaagsiekte Sheep Retrovirus (JSRV) is a betaretrovirus which is the causative agent of a contagious lung cancer in sheep called Jaagsiekte, or Ovine Pulmonary Adenocarcinoma (OPA).

JSRV is a simple retrovirus, containing the typical gag, pol, and env genes found in all retroviruses. Only one additional reading frame, termed ORF-X, is present in the JSRV genome. However, ORF-X sequences are found in the endogenous JSRV-related proviruses (carried by all sheep) which are not tumorigenic in nature. JSRV is acutely transforming, meaning it contains an oncogene capable of transforming host cells independent of genome insertion location. The viral ``env`` gene was found to transform cell cultures as well as code for protein binding motifs which are involved in cell cycle control. In addition, JSRV utilizes the Hyaluronidase-2 protein as the entry receptor. This, and other membrane-bound receptors that interact with the viral envelope protein may also be involved in the transformation process.

Like all retroviruses, the Long Terminal Repeat (LTR) of JSRV contains the virus's promoter and enhancer sequences. Once integrated, these sequences are active in Type II pneumocytes (found in the distal airways of the lung and responsible for the secretion of pulmonary surfactant) and Clara cells (found throughout the bronchiolar tree and responsible for metabolism of foreign agents.) These cells are also the likely target for JSRV-mediated transformation in the sheep.