Jaagsiekte sheep retrovirus infects multiple cell types in the ovine lung

Area of Science:

• Veterinary Pathology
• Retroviral Oncogenesis
• Comparative Pulmonary Medicine

Background:

• Ovine pulmonary adenocarcinoma (OPA) is a contagious lung cancer in sheep, driven by the Jaagsiekte sheep retrovirus (JSRV).
• The precise cell of origin for OPA remains elusive, hindering a complete understanding of its early pathogenesis.
• Mature OPA tumors exhibit markers of type II pneumocytes (SP-C) or Clara cells (CCSP), but initial JSRV infection targets are unknown.

Purpose of the Study:

• To identify the initial JSRV-infected cell types in the ovine lung during early OPA pathogenesis.
• To investigate whether JSRV targets differentiated or undifferentiated lung cells.

Main Methods:

• Experimental infection of lambs with JSRV.
• Analysis of lung tissue at early time points post-infection (10 days).
• Immunohistochemical labeling using anti-SP-C and anti-CCSP antibodies to identify infected cell types and JSRV Env protein expression.

Main Results:

• JSRV-infected cells were detected in bronchiolar and alveolar regions as early as 10 days post-infection.
• Infected cells expressed either SP-C or CCSP, confirming differentiated epithelial cells as early JSRV targets.
• Undifferentiated cells lacking SP-C or CCSP also showed JSRV Env protein expression, suggesting potential infection of progenitor cells.

Conclusions:

• Differentiated type II pneumocytes and Clara cells are early cellular targets for JSRV infection in the ovine lung.
• The findings contribute to a deeper understanding of OPA pathogenesis.
• This research offers insights relevant to human lung cancer, particularly regarding early tumor development stages.