Abstract

Ovine pulmonary adenocarcinoma (OPA) is caused by Jaagsiekte sheep retrovirus (JSRV), the causative agent of an infectious lung cancer of sheep with similarities to some forms of human lung cancer. In order to determine both the cellular origin and the pathogenesis of OPA , we analysed the phenotype of the infected and transformed cells at early and late stages of tumour development in experimentally infected lambs and adult sheep. We found that successful JSRV infection of lung cells occurs only in lambs and not in adults. JSRV infection occurs in proliferating type II pneumocytes (expressing the surfactant protein marker, SP-C) which are 50 times more abundant in young lambs compared to adult sheep. However, adult sheep subjected to mild lung injury induced by 3 methylindole (3MI), and subsequently infected by JSRV were fully susceptible to viral infection and displayed early tumour lesions. These data reinforces the notion that lung adenocarcinoma originate from progenitor alveolar cells. In addition, we showed that JSRV infection of the target cells for viral transformation occurs only in lambs or in adults after lung injury. This observation is in agreement with the common diagnosis of various bacterial, parasitic or viral infections in naturally occurring OPA cases.