Type of lung cancer

Abbreviations: ATII = alveolar type II; JSRV = jaagsiekte sheep retrovirus

The jaagsiekte sheep retrovirus (JSRV) is the causative agent of ovine pulmonary adenocarcinoma, which is the only known example of a retrovirus-induced lung cancer. The finding that the JSRV env gene is sufficient to induce the transformation of murine and avian film)blast cell lines has led to an investigation of the mechanism by which this gene induces transformation. Reports from this and other laboratories have presented conflicting data regarding the requirement for a known SH2-binding motif, which is found within the transmembrane domain of the JSRV env gene, in cellular transformation. However, these reported events have been observed in fibro blast cell lines of laboratory animals, whereas the predominant cell type transformed in the sheep host is an epithelial cell of the lung, the alveolar type II (ATII) cell.

To provide a system for investigating the effects of the JSRV envelope protein on its target cell, we report here on the isolation and extended culture (ie, 7 to 14 days) of primary sheep ATII cells, and their infection by JSRV. The maintenance of the cells in culture led to a homogeneous population of proliferating ATII cells with numerous lamellar bodies, well organized microvilli, apical/basolateral polarity, and prominent tight junctions. Moreover, the cells exhibited high levels of against-induced surfactant lipid secretion. Primary ATII cells also could be infected using the JSRV molecular clone JSRVJS7, demonstrating that the cultured cells expressed the specific receptor for JSRV, described as hyaluronidase-2, Furthermore, the viral genome was shown to be transcribed and translated as demonstrated by reverse transcriptase activity in the supernatant of virus-adsorbed cells. The examination of the effects of the JSRV envelope protein expressed in primary ATII cells and its role in ovine pulmonary adenocarcinoma is the current focus of our work.

* From the Department of Microbiology, Immunology, & Pathology (Drs. DeMartini, Ms. Platt and Mr. Allen) Colorado State University, Fort Collins, CO; and National Jewish Medical and Research Center (Ms. Evans and Mr. Voelker), Denver, CO.

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Correspondence to: James C. DeMartini, DVM, PhD, Department of Microbiology, Immunology, and Pathology, Colorado State University, 1619 Campus Delivery, Fort Collins, CO 80523-1619; e-mail: james.demartini@colostate.edu